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{{Short description|Protein which in humans is encoded by the SDC1 gene}}
{{Infobox_gene}}
{{Infobox_gene}}
{{too short|date=November 2016}}
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'''Syndecan 1''' is a [[protein]] which in humans is encoded by the ''SDC1'' [[gene]].<ref name="pmid2324102">{{cite journal | vauthors = Mali M, Jaakkola P, Arvilommi AM, Jalkanen M | title = Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans | journal = The Journal of Biological Chemistry | volume = 265 | issue = 12 | pages = 6884–9 | date = April 1990 | pmid = 2324102 | doi = | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=2324102 }}</ref><ref name="pmid2173154">{{cite journal | vauthors = Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J | title = Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2 | journal = Somatic Cell and Molecular Genetics | volume = 16 | issue = 5 | pages = 501–5 | date = September 1990 | pmid = 2173154 | doi = 10.1007/BF01233200 }}</ref>


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'''Syndecan 1''' is a [[protein]] which in humans is encoded by the ''SDC1'' [[gene]].<ref name="pmid2324102">{{cite journal | vauthors = Mali M, Jaakkola P, Arvilommi AM, Jalkanen M | title = Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans | journal = The Journal of Biological Chemistry | volume = 265 | issue = 12 | pages = 6884–6889 | date = April 1990 | pmid = 2324102 | doi = 10.1016/S0021-9258(19)39232-4 | doi-access = free }}</ref><ref name="pmid2173154">{{cite journal | vauthors = Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J | title = Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2 | journal = Somatic Cell and Molecular Genetics | volume = 16 | issue = 5 | pages = 501–505 | date = September 1990 | pmid = 2173154 | doi = 10.1007/BF01233200 | s2cid = 43270934 }}</ref> The protein is a transmembrane (type I) [[heparan sulfate]] [[proteoglycan]] and is a member of the [[syndecan]] proteoglycan family. The syndecan-1 protein functions as an [[integral membrane protein]] and participates in [[cell growth|cell proliferation]], [[cell migration]] and [[cell junction|cell-matrix]] interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines,<ref>{{cite journal | vauthors = Götte M | title = Syndecans in inflammation | journal = FASEB Journal | volume = 17 | issue = 6 | pages = 575–591 | date = April 2003 | pmid = 12665470 | doi = 10.1096/fj.02-0739rev | doi-access = free | s2cid = 16948257 }}</ref> with binding largely via heparan sulfate chains. The syndecans mediate cell binding, [[cell signaling]], and [[cytoskeleton|cytoskeletal]] organization and syndecan receptors are required for internalization of the [[HIV| HIV-1]] [[Tat (HIV)|tat protein]].
== Function ==


Altered syndecan-1 expression has been detected in several different tumor types. Syndecan 1 can be a marker for [[plasma cell]]s.
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The protein encoded by this gene is a transmembrane (type I) [[heparan sulfate]] [[proteoglycan]] and is a member of the [[syndecan]] proteoglycan family. The syndecan-1 core protein consists of an extracellular domain which can be substituted with [[heparan sulfate]] and [[chondroitin sulfate]] [[glycosaminoglycan]] chains, a highly conserved transmembrane domain, and a highly conserved cytoplasmic domain, which contains two constant regions that are separated by a variable region. <ref>{{cite journal | vauthors = Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M | title = Functions of cell surface heparan sulfate proteoglycans | journal = Annual Review of Biochemistry | volume = 68 | pages = 729–77 | date = 1999 | pmid = 10872465 | doi = 10.1146/annurev.biochem.68.1.729 }}</ref> The extracellular domain can be cleaved (shed) from the cell surface at a juxtamembrane site <ref>{{cite journal | vauthors = Wang Z, Götte M, Bernfield M, Reizes O | title = Constitutive and accelerated shedding of murine syndecan-1 is mediated by cleavage of its core protein at a specific juxtamembrane site | journal = Biochemistry | volume = 44 | issue = 37 | pages = 12355–61 | date = September 2005 | pmid = 16156648 | pmc = 2546870 | doi = 10.1021/bi050620i }}</ref>, converting the membrane-bound proteoglycan into a paracrine effector molecule with roles in wound repair <ref>{{cite journal | vauthors = Elenius V, Götte M, Reizes O, Elenius K, Bernfield M | title = Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1 | journal = The Journal of Biological Chemistry | volume = 279 | issue = 40 | pages = 41928–35 | date = October 2004 | pmid = 15220342 | doi = 10.1074/jbc.M404506200 }}</ref>and invasive growth of cancer cells. <ref>{{cite journal | vauthors = Piperigkou Z, Mohr B, Karamanos N, Götte M | title = Shed proteoglycans in tumor stroma | journal = Cell and Tissue Research | volume = 365 | issue = 3 | pages = 643–55 | date = September 2016 | pmid = 27365088 | doi = 10.1007/s00441-016-2452-4 }}</ref> The syndecans mediate cell binding, [[cell signaling]], and [[cytoskeleton|cytoskeletal]] organization and syndecan receptors are required for internalization of the [[HIV| HIV-1]] [[Tat (HIV)|tat protein]]. The syndecan-1 protein functions as an [[integral membrane protein]] and participates in [[cell growth|cell proliferation]], [[cell migration]] and [[cell junction|cell-matrix]] interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines<ref>{{cite journal | vauthors = Götte M | title = Syndecans in inflammation | journal = FASEB Journal | volume = 17 | issue = 6 | pages = 575–91 | date = April 2003 | pmid = 12665470 | doi = 10.1096/fj.02-0739rev }}</ref>, with binding largely via [[heparan sulfate]] chains.


== Structure ==
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An exception is the prosecretory mitogen [[lacritin]] that binds syndecan-1 only after heparanase modification.<ref name="pmid16982797">{{cite journal | vauthors = Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW | display-authors = 6 | title = Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin | journal = The Journal of Cell Biology | volume = 174 | issue = 7 | pages = 1097–106 | date = September 2006 | pmid = 16982797 | pmc = 1666580 | doi = 10.1083/jcb.200511134 }}</ref><ref name="pmid23504321 [PubMed - indexed for MEDLINE]">{{cite journal | vauthors = Zhang Y, Wang N, Raab RW, McKown RL, Irwin JA, Kwon I, van Kuppevelt TH, Laurie GW | display-authors = 6 | title = Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity | journal = The Journal of Biological Chemistry | volume = 288 | issue = 17 | pages = 12090–101 | date = April 2013 | pmid = 23504321 | pmc = 3636894 | doi = 10.1074/jbc.M112.422717 }}</ref> Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial [[heparanase]] (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.<ref name="pmid16982797" /> Three SDC1 elements are required. (1) The heparanase-exposed hydrophobic sequence GAGAL that promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix form and likely binds to the hydrophobic face. (2) Heparanase-cleaved heparan sulfate that is 3-O sulfated.<ref name="pmid23504321 [PubMed - indexed for MEDLINE]" /> This likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix. (3) An N-terminal [[chondroitin sulfate]] chain that also likely binds to the cationic face. Point mutagenesis of lacritin has narrowed the ligation site.<ref name="pmid23504321 [PubMed - indexed for MEDLINE]" />


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The syndecan-1 core protein consists of an extracellular domain which can be substituted with heparan sulfate and [[chondroitin sulfate]] [[glycosaminoglycan]] chains, a highly conserved transmembrane domain, and a highly conserved cytoplasmic domain, which contains two constant regions that are separated by a variable region.<ref>{{cite journal | vauthors = Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M | title = Functions of cell surface heparan sulfate proteoglycans | journal = Annual Review of Biochemistry | volume = 68 | pages = 729–777 | date = 1999 | pmid = 10872465 | doi = 10.1146/annurev.biochem.68.1.729 }}</ref> The extracellular domain can be cleaved (shed) from the cell surface at a juxtamembrane site,<ref>{{cite journal | vauthors = Wang Z, Götte M, Bernfield M, Reizes O | title = Constitutive and accelerated shedding of murine syndecan-1 is mediated by cleavage of its core protein at a specific juxtamembrane site | journal = Biochemistry | volume = 44 | issue = 37 | pages = 12355–12361 | date = September 2005 | pmid = 16156648 | pmc = 2546870 | doi = 10.1021/bi050620i }}</ref> converting the membrane-bound proteoglycan into a paracrine effector molecule with roles in wound repair <ref>{{cite journal | vauthors = Elenius V, Götte M, Reizes O, Elenius K, Bernfield M | title = Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1 | journal = The Journal of Biological Chemistry | volume = 279 | issue = 40 | pages = 41928–41935 | date = October 2004 | pmid = 15220342 | doi = 10.1074/jbc.M404506200 | doi-access = free }}</ref> and invasive growth of cancer cells.<ref>{{cite journal | vauthors = Piperigkou Z, Mohr B, Karamanos N, Götte M | title = Shed proteoglycans in tumor stroma | journal = Cell and Tissue Research | volume = 365 | issue = 3 | pages = 643–655 | date = September 2016 | pmid = 27365088 | doi = 10.1007/s00441-016-2452-4 | s2cid = 13944019 | url = https://zenodo.org/record/3375516 }}</ref>
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While several [[transcript variant|transcript]] variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.<ref>{{cite web | title = Entrez Gene: SDC1 syndecan 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6382| access-date = }}</ref>


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An exception is the prosecretory mitogen [[lacritin]] that binds syndecan-1 only after heparanase modification.<ref name="pmid16982797">{{cite journal | vauthors = Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW | display-authors = 6 | title = Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin | journal = The Journal of Cell Biology | volume = 174 | issue = 7 | pages = 1097–1106 | date = September 2006 | pmid = 16982797 | pmc = 1666580 | doi = 10.1083/jcb.200511134 }}</ref><ref name="pmid23504321 [PubMed - indexed for MEDLINE]">{{cite journal | vauthors = Zhang Y, Wang N, Raab RW, McKown RL, Irwin JA, Kwon I, van Kuppevelt TH, Laurie GW | display-authors = 6 | title = Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity | journal = The Journal of Biological Chemistry | volume = 288 | issue = 17 | pages = 12090–12101 | date = April 2013 | pmid = 23504321 | pmc = 3636894 | doi = 10.1074/jbc.M112.422717 | doi-access = free }}</ref> Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial [[heparanase]] (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.<ref name="pmid16982797" /> Three SDC1 elements are required. (1) The heparanase-exposed hydrophobic sequence GAGAL that promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix form and likely binds to the hydrophobic face. (2) Heparanase-cleaved heparan sulfate that is 3-O sulfated.<ref name="pmid23504321 [PubMed - indexed for MEDLINE]" /> This likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix. (3) An N-terminal chondroitin sulfate chain that also likely binds to the cationic face. Point mutagenesis of lacritin has narrowed the ligation site.<ref name="pmid23504321 [PubMed - indexed for MEDLINE]" />
==Studies in syndecan-1-deficient ([[knockout mice|knockout ]]) mice ==
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'''Role in [[inflammation]]'''. Syndecan-1 deficient mice show increased inflammation, which was attributed to an increased [[ICAM-1]] and [[heparan sulfate]]-dependent recruitment of [[leukocytes]] (including [[neutrophils]] and [[dendritic cells]])<ref>{{cite journal | vauthors = Averbeck M, Kuhn S, Bühligen J, Götte M, Simon JC, Polte T | title = Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens | journal = Experimental Dermatology | volume = 26 | issue = 11 | pages = 1060–1067 | date = November 2017 | pmid = 28453867 | doi = 10.1111/exd.13374 }}</ref>to the inflamed [[endothelium]]. <ref>{{cite journal | vauthors = Götte M, Joussen AM, Klein C, Andre P, Wagner DD, Hinkes MT, Kirchhof B, Adamis AP, Bernfield M | display-authors = 6 | title = Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature | journal = Investigative Ophthalmology & Visual Science | volume = 43 | issue = 4 | pages = 1135–41 | date = April 2002 | pmid = 11923257 | url = https://iovs.arvojournals.org/article.aspx?articleid=2200171 }}</ref> This increase results in higher inflammatory responses and tissue damage in experimental models of [[contact dermatitis]]<ref>{{cite journal | vauthors = Kharabi Masouleh B, Ten Dam GB, Wild MK, Seelige R, van der Vlag J, Rops AL, Echtermeyer FG, Vestweber D, van Kuppevelt TH, Kiesel L, Götte M | display-authors = 6 | title = Role of the heparan sulfate proteoglycan syndecan-1 (CD138) in delayed-type hypersensitivity | journal = Journal of Immunology | volume = 182 | issue = 8 | pages = 4985–93 | date = April 2009 | pmid = 19342678 | doi = 10.4049/jimmunol.0800574 }}</ref> , inflammation of the [[kidney]] <ref>{{cite journal | vauthors = Rops AL, Götte M, Baselmans MH, van den Hoven MJ, Steenbergen EJ, Lensen JF, Wijnhoven TJ, Cevikbas F, van den Heuvel LP, van Kuppevelt TH, Berden JH, van der Vlag J | display-authors = 6 | title = Syndecan-1 deficiency aggravates anti-glomerular basement membrane nephritis | journal = Kidney International | volume = 72 | issue = 10 | pages = 1204–15 | date = November 2007 | pmid = 17805240 | doi = 10.1038/sj.ki.5002514 }}</ref>, [[myocardial infarction]] <ref>{{cite journal | vauthors = Vanhoutte D, Schellings MW, Götte M, Swinnen M, Herias V, Wild MK, Vestweber D, Chorianopoulos E, Cortés V, Rigotti A, Stepp MA, Van de Werf F, Carmeliet P, Pinto YM, Heymans S | display-authors = 6 | title = Increased expression of syndecan-1 protects against cardiac dilatation and dysfunction after myocardial infarction | journal = Circulation | volume = 115 | issue = 4 | pages = 475–82 | date = January 2007 | pmid = 17242279 | doi = 10.1161/CIRCULATIONAHA.106.644609 }}</ref>, [[inflammatory bowel disease]] <ref>{{cite journal | vauthors = Floer M, Götte M, Wild MK, Heidemann J, Gassar ES, Domschke W, Kiesel L, Luegering A, Kucharzik T | display-authors = 6 | title = Enoxaparin improves the course of dextran sodium sulfate-induced colitis in syndecan-1-deficient mice | journal = The American Journal of Pathology | volume = 176 | issue = 1 | pages = 146–57 | date = January 2010 | pmid = 20008145 | doi = 10.2353/ajpath.2010.080639 | pmc = 2797877 }}</ref> and [[experimental autoimmune encephalomyelitis]] <ref>{{cite journal | vauthors = Zhang X, Wu C, Song J, Götte M, Sorokin L | title = Syndecan-1, a cell surface proteoglycan, negatively regulates initial leukocyte recruitment to the brain across the choroid plexus in murine experimental autoimmune encephalomyelitis | journal = Journal of Immunology | volume = 191 | issue = 9 | pages = 4551–61 | date = November 2013 | pmid = 24078687 | doi = 10.4049/jimmunol.1300931 }}</ref> In experimental [[colitis]]-induced [[colon carcinoma]], syndecan-1 deficiency promotes tumor growth in an [[interleukin-6|IL-6]] / [[STAT protein|STAT ]]-signaling-dependent manner. <ref>{{cite journal | vauthors = Binder Gallimidi A, Nussbaum G, Hermano E, Weizman B, Meirovitz A, Vlodavsky I, Götte M, Elkin M | display-authors = 6 | title = Syndecan-1 deficiency promotes tumor growth in a murine model of colitis-induced colon carcinoma | journal = PloS One | volume = 12 | issue = 3 | pages = e0174343 | date = 2017 | pmid = 28350804 | doi = 10.1371/journal.pone.0174343 }}</ref>


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While several [[transcript variant|transcript]] variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.<ref>{{cite web | title = Entrez Gene: SDC1 syndecan 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6382}}</ref>
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==Clinical significance==
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Altered syndecan-1 expression has been detected in several different tumor types.<ref>{{cite journal | vauthors = Yip GW, Smollich M, Götte M | title = Therapeutic value of glycosaminoglycans in cancer | journal = Molecular Cancer Therapeutics | volume = 5 | issue = 9 | pages = 2139–48 | date = September 2006 | pmid = 16985046 | doi = 10.1158/1535-7163.MCT-06-0082 }}</ref> <ref>{{cite journal | vauthors = Stepp MA, Pal-Ghosh S, Tadvalkar G, Pajoohesh-Ganji A | title = Syndecan-1 and Its Expanding List of Contacts | journal = Advances in Wound Care | volume = 4 | issue = 4 | pages = 235–249 | date = April 2015 | pmid = 25945286 | doi = 10.1089/wound.2014.0555 }}</ref>In [[breast cancer]], syndecan-1 is upregulated and contributes to the [[cancer stem cell]] phenotype, which is linked to increased resistance to [[chemotherapy]] and radiation therapy <ref>{{cite journal | vauthors = Hassan H, Greve B, Pavao MS, Kiesel L, Ibrahim SA, Götte M | title = Syndecan-1 modulates β-integrin-dependent and interleukin-6-dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation | journal = The FEBS Journal | volume = 280 | issue = 10 | pages = 2216–27 | date = May 2013 | pmid = 23289672 | doi = 10.1111/febs.12111 }}</ref><ref>{{cite journal | vauthors = Ibrahim SA, Gadalla R, El-Ghonaimy EA, Samir O, Mohamed HT, Hassan H, Greve B, El-Shinawi M, Mohamed MM, Götte M | display-authors = 6 | title = Syndecan-1 is a novel molecular marker for triple negative inflammatory breast cancer and modulates the cancer stem cell phenotype via the IL-6/STAT3, Notch and EGFR signaling pathways | journal = Molecular Cancer | volume = 16 | issue = 1 | pages = 57 | date = March 2017 | pmid = 28270211 | pmc = 5341174 | doi = 10.1186/s12943-017-0621-z }}</ref><ref>{{cite journal | vauthors = Götte M, Kersting C, Ruggiero M, Tio J, Tulusan AH, Kiesel L, Wülfing P | title = Predictive value of syndecan-1 expression for the response to neoadjuvant chemotherapy of primary breast cancer | journal = Anticancer Research | volume = 26 | issue = 1B | pages = 621–7 | date = 2006 | pmid = 16739330 | url = http://ar.iiarjournals.org/content/26/1B/621.long }}</ref>


==Inflammation ==
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It is a specific antigen on [[multiple myeloma]] cells.<ref name=ASH2013>[http://www.myelomabeacon.com/resources/mtgs/ash2013/abs/758/ Indatuximab Ravtansine (BT062) In Combination With Lenalidomide and Low-Dose Dexamethasone In Patients With Relapsed and/Or Refractory Multiple Myeloma: Clinical Activity In Len/Dex-Refractory Patients]</ref>
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Syndecan-1 deficient mice show increased inflammation, which was attributed to an increased [[ICAM-1]] and heparan sulfate-dependent recruitment of [[leukocytes]] (including [[neutrophils]] and [[dendritic cells]])<ref>{{cite journal | vauthors = Averbeck M, Kuhn S, Bühligen J, Götte M, Simon JC, Polte T | title = Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens | journal = Experimental Dermatology | volume = 26 | issue = 11 | pages = 1060–1067 | date = November 2017 | pmid = 28453867 | doi = 10.1111/exd.13374 | s2cid = 38757296 }}</ref> to the inflamed [[endothelium]].<ref>{{cite journal | vauthors = Götte M, Joussen AM, Klein C, Andre P, Wagner DD, Hinkes MT, Kirchhof B, Adamis AP, Bernfield M | display-authors = 6 | title = Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature | journal = Investigative Ophthalmology & Visual Science | volume = 43 | issue = 4 | pages = 1135–1141 | date = April 2002 | pmid = 11923257 | url = https://iovs.arvojournals.org/article.aspx?articleid=2200171 }}</ref> This increase results in higher inflammatory responses and tissue damage in experimental models of [[contact dermatitis]],<ref>{{cite journal | vauthors = Kharabi Masouleh B, Ten Dam GB, Wild MK, Seelige R, van der Vlag J, Rops AL, Echtermeyer FG, Vestweber D, van Kuppevelt TH, Kiesel L, Götte M | display-authors = 6 | title = Role of the heparan sulfate proteoglycan syndecan-1 (CD138) in delayed-type hypersensitivity | journal = Journal of Immunology | volume = 182 | issue = 8 | pages = 4985–4993 | date = April 2009 | pmid = 19342678 | doi = 10.4049/jimmunol.0800574 | doi-access = free }}</ref> inflammation of the [[kidney]],<ref>{{cite journal | vauthors = Rops AL, Götte M, Baselmans MH, van den Hoven MJ, Steenbergen EJ, Lensen JF, Wijnhoven TJ, Cevikbas F, van den Heuvel LP, van Kuppevelt TH, Berden JH, van der Vlag J | display-authors = 6 | title = Syndecan-1 deficiency aggravates anti-glomerular basement membrane nephritis | journal = Kidney International | volume = 72 | issue = 10 | pages = 1204–1215 | date = November 2007 | pmid = 17805240 | doi = 10.1038/sj.ki.5002514 | doi-access = free }}</ref> [[myocardial infarction]],<ref>{{cite journal | vauthors = Vanhoutte D, Schellings MW, Götte M, Swinnen M, Herias V, Wild MK, Vestweber D, Chorianopoulos E, Cortés V, Rigotti A, Stepp MA, Van de Werf F, Carmeliet P, Pinto YM, Heymans S | display-authors = 6 | title = Increased expression of syndecan-1 protects against cardiac dilatation and dysfunction after myocardial infarction | journal = Circulation | volume = 115 | issue = 4 | pages = 475–482 | date = January 2007 | pmid = 17242279 | doi = 10.1161/CIRCULATIONAHA.106.644609 | doi-access = free | url = https://lirias.kuleuven.be/bitstream/123456789/24985/1/SDC1-MMI%20d%20vanhoutte%20et%20al%200107.pdf }}</ref> [[inflammatory bowel disease]]<ref>{{cite journal | vauthors = Floer M, Götte M, Wild MK, Heidemann J, Gassar ES, Domschke W, Kiesel L, Luegering A, Kucharzik T | display-authors = 6 | title = Enoxaparin improves the course of dextran sodium sulfate-induced colitis in syndecan-1-deficient mice | journal = The American Journal of Pathology | volume = 176 | issue = 1 | pages = 146–157 | date = January 2010 | pmid = 20008145 | pmc = 2797877 | doi = 10.2353/ajpath.2010.080639 }}</ref> and [[experimental autoimmune encephalomyelitis]]<ref>{{cite journal | vauthors = Zhang X, Wu C, Song J, Götte M, Sorokin L | title = Syndecan-1, a cell surface proteoglycan, negatively regulates initial leukocyte recruitment to the brain across the choroid plexus in murine experimental autoimmune encephalomyelitis | journal = Journal of Immunology | volume = 191 | issue = 9 | pages = 4551–4561 | date = November 2013 | pmid = 24078687 | doi = 10.4049/jimmunol.1300931 | doi-access = free }}</ref> In experimental [[colitis]]-induced [[colon carcinoma]], syndecan-1 deficiency promotes tumor growth in an [[interleukin-6|IL-6]] / [[STAT protein|STAT]]-signaling-dependent manner.<ref>{{cite journal | vauthors = Binder Gallimidi A, Nussbaum G, Hermano E, Weizman B, Meirovitz A, Vlodavsky I, Götte M, Elkin M | display-authors = 6 | title = Syndecan-1 deficiency promotes tumor growth in a murine model of colitis-induced colon carcinoma | journal = PLOS ONE | volume = 12 | issue = 3 | pages = e0174343 | date = 2017 | pmid = 28350804 | pmc = 5369774 | doi = 10.1371/journal.pone.0174343 | doi-access = free | bibcode = 2017PLoSO..1274343B }}</ref>


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==Clinical significance==
[[Indatuximab ravtansine]] targets this protein.
⚫
Altered syndecan-1 expression has been detected in several different tumor types.<ref>{{cite journal | vauthors = Yip GW, Smollich M, Götte M | title = Therapeutic value of glycosaminoglycans in cancer | journal = Molecular Cancer Therapeutics | volume = 5 | issue = 9 | pages = 2139–2148 | date = September 2006 | pmid = 16985046 | doi = 10.1158/1535-7163.MCT-06-0082 | doi-access = free | url = https://aacr.figshare.com/articles/journal_contribution/Supplementary_Table_S1_from_Therapeutic_value_of_glycosaminoglycans_in_cancer/22484577/1/files/39936114.pdf }}</ref><ref>{{cite journal | vauthors = Stepp MA, Pal-Ghosh S, Tadvalkar G, Pajoohesh-Ganji A | title = Syndecan-1 and Its Expanding List of Contacts | journal = Advances in Wound Care | volume = 4 | issue = 4 | pages = 235–249 | date = April 2015 | pmid = 25945286 | pmc = 4397989 | doi = 10.1089/wound.2014.0555 }}</ref> In [[breast cancer]], syndecan-1 is up regulated and contributes to the [[cancer stem cell]] phenotype, which is linked to increased resistance to [[chemotherapy]] and radiation therapy <ref>{{cite journal | vauthors = Hassan H, Greve B, Pavao MS, Kiesel L, Ibrahim SA, Götte M | title = Syndecan-1 modulates β-integrin-dependent and interleukin-6-dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation | journal = The FEBS Journal | volume = 280 | issue = 10 | pages = 2216–2227 | date = May 2013 | pmid = 23289672 | doi = 10.1111/febs.12111 | s2cid = 19929711 | doi-access = }}</ref><ref>{{cite journal | vauthors = Ibrahim SA, Gadalla R, El-Ghonaimy EA, Samir O, Mohamed HT, Hassan H, Greve B, El-Shinawi M, Mohamed MM, Götte M | display-authors = 6 | title = Syndecan-1 is a novel molecular marker for triple negative inflammatory breast cancer and modulates the cancer stem cell phenotype via the IL-6/STAT3, Notch and EGFR signaling pathways | journal = Molecular Cancer | volume = 16 | issue = 1 | pages = 57 | date = March 2017 | pmid = 28270211 | pmc = 5341174 | doi = 10.1186/s12943-017-0621-z | doi-access = free }}</ref><ref>{{cite journal | vauthors = Götte M, Kersting C, Ruggiero M, Tio J, Tulusan AH, Kiesel L, Wülfing P | title = Predictive value of syndecan-1 expression for the response to neoadjuvant chemotherapy of primary breast cancer | journal = Anticancer Research | volume = 26 | issue = 1B | pages = 621–627 | date = 2006 | pmid = 16739330 | url = http://ar.iiarjournals.org/content/26/1B/621.long }}</ref>


⚫
It is a specific antigen on [[multiple myeloma]] cells.<ref name=ASH2013>[http://www.myelomabeacon.com/resources/mtgs/ash2013/abs/758/ Indatuximab Ravtansine (BT062) In Combination With Lenalidomide and Low-Dose Dexamethasone In Patients With Relapsed and/Or Refractory Multiple Myeloma: Clinical Activity In Len/Dex-Refractory Patients]</ref> [[Indatuximab ravtansine]] targets this protein.
⚫
== Application ==


⚫
== Application ==
It is a useful marker for [[plasma cell]]s,<ref name="pmid18770841">{{cite journal | vauthors = Rawstron AC | title = Immunophenotyping of plasma cells | journal = Current Protocols in Cytometry | volume = Chapter 6 | issue = 1 | pages = Unit6.23 | date = May 2006 | pmid = 18770841 | doi = 10.1002/0471142956.cy0623s36 }}</ref> but only if the cells tested are already known to be derived from blood.<ref name="pmid14983940">{{cite journal | vauthors = O'Connell FP, Pinkus JL, Pinkus GS | title = CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms | journal = American Journal of Clinical Pathology | volume = 121 | issue = 2 | pages = 254–63 | date = February 2004 | pmid = 14983940 | doi = 10.1309/617D-WB5G-NFWX-HW4L | url = http://ajcp.metapress.com/openurl.asp?genre=article&issn=0002-9173&volume=121&issue=2&spage=254 }}{{Dead link|date=June 2018 |bot=InternetArchiveBot |fix-attempted=no }}</ref>
It is a useful marker for [[plasma cell]]s,<ref name="pmid18770841">{{cite book | vauthors = Rawstron AC | chapter = Chapter 6: Immunophenotyping of plasma cells | title = Current Protocols in Cytometry | issue = 1 | pages = Unit 6.23 | date = May 2006 | volume = Chapter 6 | pmid = 18770841 | doi = 10.1002/0471142956.cy0623s36 | isbn = 0471142956 | s2cid = 19511070 }}</ref> but only if the cells tested are already known to be derived from blood.<ref name="pmid14983940">{{cite journal | vauthors = O'Connell FP, Pinkus JL, Pinkus GS | title = CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms | journal = American Journal of Clinical Pathology | volume = 121 | issue = 2 | pages = 254–263 | date = February 2004 | pmid = 14983940 | doi = 10.1309/617D-WB5G-NFWX-HW4L | doi-access = free | author3-link = Geraldine Pinkus }}{{Dead link|date=June 2018 |bot=InternetArchiveBot |fix-attempted=no }}</ref> For plasma cells, it usually stains intensely membranous, with or without associated diffuse weak cytoplasmic and/or Golgi staining.<ref name="pmid17714757">{{cite journal | vauthors = Al-Quran SZ, Yang L, Magill JM, Braylan RC, Douglas-Nikitin VK | title = Assessment of bone marrow plasma cell infiltrates in multiple myeloma: the added value of CD138 immunohistochemistry | journal = Human Pathology | volume = 38 | issue = 12 | pages = 1779–1787 | date = December 2007 | pmid = 17714757 | pmc = 3419754 | doi = 10.1016/j.humpath.2007.04.010 }}</ref> Few cases show cytoplasmic granular staining, with or without associated Golgi staining.<ref name="pmid17714757"/>


== References ==
== References ==
{{reflist}}
{{reflist}}


== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = David G | title = Structural and functional diversity of the heparan sulfate proteoglycans | journal = Advances in Experimental Medicine and Biology | volume = 313 | issue = | pages = 69–78 | year = 1992 | pmid = 1442271 | doi = 10.1007/978-1-4899-2444-5_7 | isbn = 978-1-4899-2446-9 }}
* {{cite book | vauthors = David G | title = Heparin and Related Polysaccharides | chapter = Structural and Functional Diversity of the Heparan Sulfate Proteoglycans | series = Advances in Experimental Medicine and Biology | volume = 313 | pages = 69–78 | year = 1992 | pmid = 1442271 | doi = 10.1007/978-1-4899-2444-5_7 | isbn = 978-1-4899-2446-9 }}
* {{cite journal | vauthors = Jaakkola P, Jalkanen M | title = Transcriptional regulation of Syndecan-1 expression by growth factors | journal = Progress in Nucleic Acid Research and Molecular Biology | volume = 63 | issue = | pages = 109–38 | year = 1999 | pmid = 10506830 | doi = 10.1016/S0079-6603(08)60721-7 | isbn = 978-0-12-540063-3 | series = Progress in Nucleic Acid Research and Molecular Biology }}
* {{cite book | vauthors = Jaakkola P, Jalkanen M | title = Transcriptional regulation of Syndecan-1 expression by growth factors | volume = 63 | pages = 109–38 | year = 1999 | pmid = 10506830 | doi = 10.1016/S0079-6603(08)60721-7 | isbn = 978-0-12-540063-3 | series = Progress in Nucleic Acid Research and Molecular Biology }}
* {{cite journal | vauthors = Wijdenes J, Dore JM, Clement C, Vermot-Desroches C | title = CD138 | journal = Journal of Biological Regulators and Homeostatic Agents | volume = 16 | issue = 2 | pages = 152–5 | year = 2003 | pmid = 12144130 | doi = }}
* {{cite journal | vauthors = Wijdenes J, Dore JM, Clement C, Vermot-Desroches C | title = CD138 | journal = Journal of Biological Regulators and Homeostatic Agents | volume = 16 | issue = 2 | pages = 152–155 | year = 2003 | pmid = 12144130 }}
* {{cite journal | vauthors = Lories V, Cassiman JJ, Van den Berghe H, David G | title = Differential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cells and lung fibroblasts | journal = The Journal of Biological Chemistry | volume = 267 | issue = 2 | pages = 1116–22 | date = January 1992 | pmid = 1339431 | doi = }}
* {{cite journal | vauthors = Lories V, Cassiman JJ, Van den Berghe H, David G | title = Differential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cells and lung fibroblasts | journal = The Journal of Biological Chemistry | volume = 267 | issue = 2 | pages = 1116–1122 | date = January 1992 | pmid = 1339431 | doi = 10.1016/S0021-9258(18)48404-9 | doi-access = free }}
* {{cite journal | vauthors = Vainio S, Jalkanen M, Bernfield M, Saxén L | title = Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney | journal = Developmental Biology | volume = 152 | issue = 2 | pages = 221–32 | date = August 1992 | pmid = 1644217 | doi = 10.1016/0012-1606(92)90130-9 }}
* {{cite journal | vauthors = Vainio S, Jalkanen M, Bernfield M, Saxén L | title = Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney | journal = Developmental Biology | volume = 152 | issue = 2 | pages = 221–232 | date = August 1992 | pmid = 1644217 | doi = 10.1016/0012-1606(92)90130-9 }}
* {{cite journal | vauthors = Kiefer MC, Ishihara M, Swiedler SJ, Crawford K, Stephans JC, Barr PJ | title = The molecular biology of heparan sulfate fibroblast growth factor receptors | journal = Annals of the New York Academy of Sciences | volume = 638 | issue = | pages = 167–76 | year = 1992 | pmid = 1664683 | doi = 10.1111/j.1749-6632.1991.tb49027.x }}
* {{cite journal | vauthors = Kiefer MC, Ishihara M, Swiedler SJ, Crawford K, Stephans JC, Barr PJ | title = The molecular biology of heparan sulfate fibroblast growth factor receptors | journal = Annals of the New York Academy of Sciences | volume = 638 | pages = 167–176 | year = 1992 | pmid = 1664683 | doi = 10.1111/j.1749-6632.1991.tb49027.x | s2cid = 29216939 }}
* {{cite journal | vauthors = Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J | title = Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2 | journal = Somatic Cell and Molecular Genetics | volume = 16 | issue = 5 | pages = 501–5 | date = September 1990 | pmid = 2173154 | doi = 10.1007/BF01233200 }}
* {{cite journal | vauthors = Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J | title = Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2 | journal = Somatic Cell and Molecular Genetics | volume = 16 | issue = 5 | pages = 501–505 | date = September 1990 | pmid = 2173154 | doi = 10.1007/BF01233200 | s2cid = 43270934 }}
* {{cite journal | vauthors = Mali M, Jaakkola P, Arvilommi AM, Jalkanen M | title = Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans | journal = The Journal of Biological Chemistry | volume = 265 | issue = 12 | pages = 6884–9 | date = April 1990 | pmid = 2324102 | doi = }}
* {{cite journal | vauthors = Mali M, Jaakkola P, Arvilommi AM, Jalkanen M | title = Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans | journal = The Journal of Biological Chemistry | volume = 265 | issue = 12 | pages = 6884–6889 | date = April 1990 | pmid = 2324102 | doi = 10.1016/S0021-9258(19)39232-4 | doi-access = free }}
* {{cite journal | vauthors = Sanderson RD, Lalor P, Bernfield M | title = B lymphocytes express and lose syndecan at specific stages of differentiation | journal = Cell Regulation | volume = 1 | issue = 1 | pages = 27–35 | date = November 1989 | pmid = 2519615 | pmc = 361422 | doi = 10.1091/mbc.1.1.27 }}
* {{cite journal | vauthors = Sanderson RD, Lalor P, Bernfield M | title = B lymphocytes express and lose syndecan at specific stages of differentiation | journal = Cell Regulation | volume = 1 | issue = 1 | pages = 27–35 | date = November 1989 | pmid = 2519615 | pmc = 361422 | doi = 10.1091/mbc.1.1.27 }}
* {{cite journal | vauthors = Asundi VK, Carey DJ | title = Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region | journal = The Journal of Biological Chemistry | volume = 270 | issue = 44 | pages = 26404–10 | date = November 1995 | pmid = 7592855 | doi = 10.1074/jbc.270.44.26404 }}
* {{cite journal | vauthors = Asundi VK, Carey DJ | title = Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region | journal = The Journal of Biological Chemistry | volume = 270 | issue = 44 | pages = 26404–26410 | date = November 1995 | pmid = 7592855 | doi = 10.1074/jbc.270.44.26404 | doi-access =free }}
* {{cite journal | vauthors = Zhang L, David G, Esko JD | title = Repetitive Ser-Gly sequences enhance heparan sulfate assembly in proteoglycans | journal = The Journal of Biological Chemistry | volume = 270 | issue = 45 | pages = 27127–35 | date = November 1995 | pmid = 7592967 | doi = 10.1074/jbc.270.45.27127 }}
* {{cite journal | vauthors = Zhang L, David G, Esko JD | title = Repetitive Ser-Gly sequences enhance heparan sulfate assembly in proteoglycans | journal = The Journal of Biological Chemistry | volume = 270 | issue = 45 | pages = 27127–27135 | date = November 1995 | pmid = 7592967 | doi = 10.1074/jbc.270.45.27127 | doi-access = free }}
* {{cite journal | vauthors = Barillari G, Gendelman R, Gallo RC, Ensoli B | title = The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 17 | pages = 7941–5 | date = September 1993 | pmid = 7690138 | pmc = 47263 | doi = 10.1073/pnas.90.17.7941 | bibcode = 1993PNAS...90.7941B }}
* {{cite journal | vauthors = Barillari G, Gendelman R, Gallo RC, Ensoli B | title = The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 17 | pages = 7941–7945 | date = September 1993 | pmid = 7690138 | pmc = 47263 | doi = 10.1073/pnas.90.17.7941 | doi-access = free | bibcode = 1993PNAS...90.7941B }}
* {{cite journal | vauthors = Spring J, Goldberger OA, Jenkins NA, Gilbert DJ, Copeland NG, Bernfield M | title = Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family | journal = Genomics | volume = 21 | issue = 3 | pages = 597–601 | date = June 1994 | pmid = 7959737 | doi = 10.1006/geno.1994.1319 }}
* {{cite journal | vauthors = Spring J, Goldberger OA, Jenkins NA, Gilbert DJ, Copeland NG, Bernfield M | title = Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family | journal = Genomics | volume = 21 | issue = 3 | pages = 597–601 | date = June 1994 | pmid = 7959737 | doi = 10.1006/geno.1994.1319 }}
* {{cite journal | vauthors = Sneed TB, Stanley DJ, Young LA, Sanderson RD | title = Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells | journal = Cellular Immunology | volume = 153 | issue = 2 | pages = 456–67 | date = February 1994 | pmid = 8118875 | doi = 10.1006/cimm.1994.1042 }}
* {{cite journal | vauthors = Sneed TB, Stanley DJ, Young LA, Sanderson RD | title = Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells | journal = Cellular Immunology | volume = 153 | issue = 2 | pages = 456–467 | date = February 1994 | pmid = 8118875 | doi = 10.1006/cimm.1994.1042 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Kokenyesi R, Bernfield M | title = Core protein structure and sequence determine the site and presence of heparan sulfate and chondroitin sulfate on syndecan-1 | journal = The Journal of Biological Chemistry | volume = 269 | issue = 16 | pages = 12304–9 | date = April 1994 | pmid = 8163535 | doi = }}
* {{cite journal | vauthors = Kokenyesi R, Bernfield M | title = Core protein structure and sequence determine the site and presence of heparan sulfate and chondroitin sulfate on syndecan-1 | journal = The Journal of Biological Chemistry | volume = 269 | issue = 16 | pages = 12304–12309 | date = April 1994 | pmid = 8163535 | doi = 10.1016/S0021-9258(17)32716-3 | doi-access = free }}
* {{cite journal | vauthors = Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, Paglialunga G, Bussolino F, Noonan D | display-authors = 6 | title = HIV-tat protein is a heparin-binding angiogenic growth factor | journal = Oncogene | volume = 12 | issue = 2 | pages = 289–97 | date = January 1996 | pmid = 8570206 | doi = }}
* {{cite journal | vauthors = Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, Paglialunga G, Bussolino F, Noonan D | display-authors = 6 | title = HIV-tat protein is a heparin-binding angiogenic growth factor | journal = Oncogene | volume = 12 | issue = 2 | pages = 289–297 | date = January 1996 | pmid = 8570206 }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }}
* {{cite journal | vauthors = Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A | title = The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p | journal = Human Genetics | volume = 99 | issue = 3 | pages = 295–7 | date = March 1997 | pmid = 9050911 | doi = 10.1007/s004390050360 }}
* {{cite journal | vauthors = Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A | title = The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p | journal = Human Genetics | volume = 99 | issue = 3 | pages = 295–297 | date = March 1997 | pmid = 9050911 | doi = 10.1007/s004390050360 | s2cid = 30155082 }}
{{refend}}
{{refend}}


*
== External links ==
* {{MeshName|Syndecan-1}}


{{Clusters of differentiation}}
{{Clusters of differentiation}}

Latest revision as of 10:04, 27 March 2024

SDC1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSDC1, CD138, SDC, SYND1, syndecan, syndecan 1
External IDsOMIM: 186355; MGI: 1349162; HomoloGene: 2252; GeneCards: SDC1; OMA:SDC1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6382

20969

Ensembl

ENSG00000115884

ENSMUSG00000020592

UniProt

P18827

P18828

RefSeq (mRNA)

NM_001006946
NM_002997

NM_011519

RefSeq (protein)

NP_001006947
NP_002988

NP_035649

Location (UCSC)Chr 2: 20.2 – 20.23 MbChr 12: 8.82 – 8.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Syndecan 1 is a protein which in humans is encoded by the SDC1 gene.[5][6] The protein is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines,[7] with binding largely via heparan sulfate chains. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein.

Altered syndecan-1 expression has been detected in several different tumor types. Syndecan 1 can be a marker for plasma cells.

Structure

[edit]

The syndecan-1 core protein consists of an extracellular domain which can be substituted with heparan sulfate and chondroitin sulfate glycosaminoglycan chains, a highly conserved transmembrane domain, and a highly conserved cytoplasmic domain, which contains two constant regions that are separated by a variable region.[8] The extracellular domain can be cleaved (shed) from the cell surface at a juxtamembrane site,[9] converting the membrane-bound proteoglycan into a paracrine effector molecule with roles in wound repair [10] and invasive growth of cancer cells.[11]

An exception is the prosecretory mitogen lacritin that binds syndecan-1 only after heparanase modification.[12][13] Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.[12] Three SDC1 elements are required. (1) The heparanase-exposed hydrophobic sequence GAGAL that promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix form and likely binds to the hydrophobic face. (2) Heparanase-cleaved heparan sulfate that is 3-O sulfated.[13] This likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix. (3) An N-terminal chondroitin sulfate chain that also likely binds to the cationic face. Point mutagenesis of lacritin has narrowed the ligation site.[13]

While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.[14]

Inflammation

[edit]

Syndecan-1 deficient mice show increased inflammation, which was attributed to an increased ICAM-1 and heparan sulfate-dependent recruitment of leukocytes (including neutrophils and dendritic cells)[15] to the inflamed endothelium.[16] This increase results in higher inflammatory responses and tissue damage in experimental models of contact dermatitis,[17] inflammation of the kidney,[18] myocardial infarction,[19] inflammatory bowel disease[20] and experimental autoimmune encephalomyelitis[21] In experimental colitis-induced colon carcinoma, syndecan-1 deficiency promotes tumor growth in an IL-6 / STAT-signaling-dependent manner.[22]

Clinical significance

[edit]

Altered syndecan-1 expression has been detected in several different tumor types.[23][24] In breast cancer, syndecan-1 is up regulated and contributes to the cancer stem cell phenotype, which is linked to increased resistance to chemotherapy and radiation therapy [25][26][27]

It is a specific antigen on multiple myeloma cells.[28] Indatuximab ravtansine targets this protein.

Application

[edit]

It is a useful marker for plasma cells,[29] but only if the cells tested are already known to be derived from blood.[30] For plasma cells, it usually stains intensely membranous, with or without associated diffuse weak cytoplasmic and/or Golgi staining.[31] Few cases show cytoplasmic granular staining, with or without associated Golgi staining.[31]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115884 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020592 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Mali M, Jaakkola P, Arvilommi AM, Jalkanen M (April 1990). "Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans". The Journal of Biological Chemistry. 265 (12): 6884–6889. doi:10.1016/S0021-9258(19)39232-4. PMID 2324102.
  6. ^ Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (September 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somatic Cell and Molecular Genetics. 16 (5): 501–505. doi:10.1007/BF01233200. PMID 2173154. S2CID 43270934.
  7. ^ Götte M (April 2003). "Syndecans in inflammation". FASEB Journal. 17 (6): 575–591. doi:10.1096/fj.02-0739rev. PMID 12665470. S2CID 16948257.
  8. ^ Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M (1999). "Functions of cell surface heparan sulfate proteoglycans". Annual Review of Biochemistry. 68: 729–777. doi:10.1146/annurev.biochem.68.1.729. PMID 10872465.
  9. ^ Wang Z, Götte M, Bernfield M, Reizes O (September 2005). "Constitutive and accelerated shedding of murine syndecan-1 is mediated by cleavage of its core protein at a specific juxtamembrane site". Biochemistry. 44 (37): 12355–12361. doi:10.1021/bi050620i. PMC 2546870. PMID 16156648.
  10. ^ Elenius V, Götte M, Reizes O, Elenius K, Bernfield M (October 2004). "Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1". The Journal of Biological Chemistry. 279 (40): 41928–41935. doi:10.1074/jbc.M404506200. PMID 15220342.
  11. ^ Piperigkou Z, Mohr B, Karamanos N, Götte M (September 2016). "Shed proteoglycans in tumor stroma". Cell and Tissue Research. 365 (3): 643–655. doi:10.1007/s00441-016-2452-4. PMID 27365088. S2CID 13944019.
  12. ^ a b Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, et al. (September 2006). "Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin". The Journal of Cell Biology. 174 (7): 1097–1106. doi:10.1083/jcb.200511134. PMC 1666580. PMID 16982797.
  13. ^ a b c Zhang Y, Wang N, Raab RW, McKown RL, Irwin JA, Kwon I, et al. (April 2013). "Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity". The Journal of Biological Chemistry. 288 (17): 12090–12101. doi:10.1074/jbc.M112.422717. PMC 3636894. PMID 23504321.
  14. ^ "Entrez Gene: SDC1 syndecan 1".
  15. ^ Averbeck M, Kuhn S, Bühligen J, Götte M, Simon JC, Polte T (November 2017). "Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens". Experimental Dermatology. 26 (11): 1060–1067. doi:10.1111/exd.13374. PMID 28453867. S2CID 38757296.
  16. ^ Götte M, Joussen AM, Klein C, Andre P, Wagner DD, Hinkes MT, et al. (April 2002). "Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature". Investigative Ophthalmology & Visual Science. 43 (4): 1135–1141. PMID 11923257.
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Further reading

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