Mesothelin

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MSLN
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMSLN, MPF, SMRP, mesothelin
External IDsOMIM: 601051 MGI: 1888992 HomoloGene: 4249 GeneCards: MSLN
Gene location (Human)
Chromosome 16 (human)
Chr.Chromosome 16 (human)[1]
Chromosome 16 (human)
Genomic location for MSLN
Genomic location for MSLN
Band16p13.3Start760,762 bp[1]
End768,865 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001177355
NM_005823
NM_013404

NM_018857
NM_001356286

RefSeq (protein)

NP_001170826
NP_005814
NP_037536

NP_061345
NP_001343215

Location (UCSC)Chr 16: 0.76 – 0.77 MbChr 17: 25.75 – 25.75 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mesothelin, also known as MSLN, is a protein that in humans is encoded by the MSLN gene.[5][6]

Function[edit]

Mesothelin is a 40 kDa protein that is expressed in mesothelial cells.[7] The protein was first identified by its reactivity with monoclonal antibody K1.[8] Subsequent cloning studies showed that the mesothelin gene encodes a precursor protein that is processed to yield mesothelin which is attached to the cell membrane by a glycophosphatidylinositol linkage and a 31-kDa shed fragment named megakaryocyte-potentiating factor (MPF). Although it has been proposed that mesothelin may be involved in cell adhesion, its biological function is not known.[9] A knockout mouse line that lacks mesothelin reproduces and develops normally.[10]

Mesothelin is over expressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma.[7] The interaction between mesothelin and MUC16 (also known as CA125) may facilitate the implantation and peritoneal spread of tumors by cell adhesion. The region (296-359) consisting of 64 amino acids at the N-terminal of cell surface mesothelin is the functional binding domain for MUC16.[11]

Medical applications[edit]

Mesothelin is a tumour differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium.[12] Since mesothelin is overexpressed in several cancers and is immunogenic, the protein could be exploited as tumor marker or as the antigenic target of a therapeutic cancer vaccine.[9][12] A 2016 review indicates that some immunotherapeutic strategies have shown encouraging results in early-phase clinical trials. [13] Elevations of serum mesothelin specific to ovarian and other cancer patients may be measured using ELISA assays.[14] Assays for blood-bourne mesothelin and MPF for tumor diagnosis, especially applied to asbestos-related mesothelioma have been developed.[15] Elevated serum mesothelin was found in most patients with mesothelioma (71%) and ovarian cancer (67%).[16] Blood MPF and mesothelin levels were correlated, with modest accuracy for malignant pleural mesothelioma and lung cancer (sensitivity 74% and 59%, specificity 90% and 86%, respectively for MPF and mesothelin assays).[17] Circulating mesothelin is reported in nearly all pancreatic cancers,[18] however the levels in healthy persons often exceed 80 ng/mL (using 40 kD molecular weight as the conversion factor) and to widely overlap the values in the pancreatic cancer patients.[19] It was noted that the cutoff levels for normal could differ as much as 10-fold among publications, depending on the assay used[19][17][16] and thus that normal levels must be determined anew when new assays are introduced.

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102854 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000063011 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Kojima T, Oh-eda M, Hattori K, Taniguchi Y, Tamura M, Ochi N, Yamaguchi N (September 1995). "Molecular cloning and expression of megakaryocyte potentiating factor cDNA". J. Biol. Chem. 270 (37): 21984–90. doi:10.1074/jbc.270.37.21984. PMID 7665620. 
  6. ^ Chang K, Pastan I (January 1996). "Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers". Proc. Natl. Acad. Sci. U.S.A. 93 (1): 136–40. Bibcode:1996PNAS...93..136C. doi:10.1073/pnas.93.1.136. PMC 40193Freely accessible. PMID 8552591. 
  7. ^ a b Hassan R, Ho M (January 2008). "Mesothelin targeted cancer immunotherapy". European Journal of Cancer. 44 (1): 46–53. doi:10.1016/j.ejca.2007.08.028. PMC 2265108Freely accessible. PMID 17945478. 
  8. ^ Chang K, Pai LH, Batra JK, Pastan I, Willingham MC (January 1992). "Characterization of the antigen (CAK1) recognized by monoclonal antibody K1 present on ovarian cancers and normal mesothelium". Cancer Research. 52 (1): 181–6. PMID 1727378. 
  9. ^ a b Hassan R, Bera T, Pastan I (June 2004). "Mesothelin: a new target for immunotherapy". Clinical Cancer Research. 10 (12 Pt 1): 3937–42. doi:10.1158/1078-0432.CCR-03-0801. PMID 15217923. 
  10. ^ Bera TK, Pastan I (2000). "Mesothelin is not required for normal mouse development or reproduction". Molecular and Cellular Biology. 20 (8): 2902–6. doi:10.1128/MCB.20.8.2902-2906.2000. PMC 85523Freely accessible. PMID 10733593. 
  11. ^ Kaneko O, Gong L, Zhang J, Hansen JK, Hassan R, Lee B, Ho M (February 2009). "A binding domain on mesothelin for CA125/MUC16". The Journal of Biological Chemistry. 284 (6): 3739–49. doi:10.1074/jbc.M806776200. PMC 2635045Freely accessible. PMID 19075018. 
  12. ^ a b Hassan R, Ho M (January 2008). "Mesothelin targeted cancer immunotherapy". Eur. J. Cancer. 44 (1): 46–53. doi:10.1016/j.ejca.2007.08.028. PMC 2265108Freely accessible. PMID 17945478. 
  13. ^ Morello A, Sadelain M, Adusumilli PS (2016). "Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors". Cancer Discovery. 6 (2): 133–46. doi:10.1158/2159-8290.CD-15-0583. PMC 4744527Freely accessible. PMID 26503962. 
  14. ^ Scholler N, Fu N, Yang Y, Ye Z, Goodman GE, Hellström KE, Hellström I (September 1999). "Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma". Proc. Natl. Acad. Sci. U.S.A. 96 (20): 11531–6. Bibcode:1999PNAS...9611531S. doi:10.1073/pnas.96.20.11531. PMC 18068Freely accessible. PMID 10500211. 
  15. ^ Maeda M, Hino O (2006). "Blood tests for asbestos-related mesothelioma". Oncology. 71 (1–2): 26–31. doi:10.1159/000100446. PMID 17344668. 
  16. ^ a b Hassan R, Remaley AT, Sampson ML, Zhang J, Cox DD, Pingpank J, Alexander R, Willingham M, Pastan I, Onda M (January 2006). "Detection and quantitation of serum mesothelin, a tumor marker for patients with mesothelioma and ovarian cancer". Clin. Cancer Res. 12 (2): 447–53. doi:10.1158/1078-0432.CCR-05-1477. PMID 16428485. 
  17. ^ a b Iwahori K, Osaki T, Serada S, Fujimoto M, Suzuki H, Kishi Y, Yokoyama A, Hamada H, Fujii Y, Yamaguchi K, Hirashima T, Matsui K, Tachibana I, Nakamura Y, Kawase I, Naka T (October 2008). "Megakaryocyte potentiating factor as a tumor marker of malignant pleural mesothelioma: evaluation in comparison with mesothelin". Lung Cancer. 62 (1): 45–54. doi:10.1016/j.lungcan.2008.02.012. PMID 18394747. 
  18. ^ Johnston FM, Tan MC, Tan BR, Porembka MR, Brunt EM, Linehan DC, Simon PO, Plambeck-Suess S, Eberlein TJ, Hellstrom KE, Hellstrom I, Hawkins WG, Goedegebuure P (November 2009). "Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer". Clin. Cancer Res. 15 (21): 6511–8. doi:10.1158/1078-0432.CCR-09-0565. PMC 2782601Freely accessible. PMID 19843662. 
  19. ^ a b Sharon E, Zhang J, Hollevoet K, Steinberg SM, Pastan I, Onda M, Gaedcke J, Ghadimi BM, Ried T, Hassan R (April 2012). "Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers". Clin. Chem. Lab. Med. 50 (4): 721–5. doi:10.1515/CCLM.2011.816. PMID 22149739. 

Further reading[edit]

External links[edit]