CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and tumor marker.
This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the activation of NF-kappaB. It is a positive regulator of apoptosis, and also has been shown to limit the proliferative potential of autoreactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.[1]
CD30 is associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma but not in seminoma and is thus a useful marker in distinguishing between these germ cell tumors.[2] CD30 and CD15 are also expressed on classical Hodgkin Lymphoma Reed-Sternberg cells.[3]
Interactions[edit]
CD30 has been shown to interact with TRAF5,[4] TRAF1,[5] TRAF2[4][5] and TRAF3.[5]
Cancer Treatment[edit]
CD30 is the target of the FDA approved therapeutic Brentuximab Vedotin (Adcetris), designed and developed by Seattle Genetics. It is approved for use in:
1) Hodgkin lymphoma (HL) (brentuximab vedotin) after failure of autologous stem cell transplant (ASCT)
2) HL in patients who are not ASCT candidates after failure of at least 2 multiagent chemotherapy regimens
3) Systemic anaplastic large cell lymphoma (sALCL) after failure of at least 1 multiagent chemotherapy regimen [6]
References[edit]
- ^ "Entrez Gene: TNFRSF8 tumor necrosis factor receptor superfamily, member 8".
- ^ Teng LH, Lu DH, Xu QZ, Fu YJ, Yang H, He ZL (2005). "[Expression and diagnostic significance of OCT4, CD117 and CD30 in germ cell tumors]". Zhonghua Bing Li Xue Za Zhi (in Chinese) 34 (11): 711–5. PMID 16536313.
- ^ Gorczyca W, Tsang P, Liu Z, et al. (February 2003). "CD30-positive T-cell lymphomas co-expressing CD15: an immunohistochemical analysis". Int. J. Oncol. 22 (2): 319–24. PMID 12527929.
- ^ a b Aizawa, S; Nakano H, Ishida T, Horie R, Nagai M, Ito K, Yagita H, Okumura K, Inoue J, Watanabe T (January 1997). "Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation". J. Biol. Chem. 272 (4): 2042–5. doi:10.1074/jbc.272.4.2042. PMID 8999898.
- ^ a b c Ansieau, S; Scheffrahn I, Mosialos G, Brand H, Duyster J, Kaye K, Harada J, Dougall B, Hübinger G, Kieff E, Herrmann F, Leutz A, Gruss H J (November 1996). "Tumor necrosis factor receptor-associated factor (TRAF)-1, TRAF-2, and TRAF-3 interact in vivo with the CD30 cytoplasmic domain; TRAF-2 mediates CD30-induced nuclear factor kappa B activation". Proc. Natl. Acad. Sci. U.S.A. 93 (24): 14053–8. doi:10.1073/pnas.93.24.14053. PMC 19493. PMID 8943059. (Retracted. If this is intentional, please replace
{{Retracted}} with {{Retracted|intentional=yes}}.)
- ^ Changchun, Deng; Beiqun Pan, Owen A. O'Connor (15). "Brentuximab Vedotin". Clinical Cancer Research 19: 22. PMID 23155186.
Further reading[edit]
- Schneider C, Hübinger G (2003). "Pleiotropic signal transduction mediated by human CD30: a member of the tumor necrosis factor receptor (TNFR) family". Leuk. Lymphoma 43 (7): 1355–66. doi:10.1080/10428190290033288. PMID 12389614.
- Horie R, Higashihara M, Watanabe T (2003). "Hodgkin's lymphoma and CD30 signal transduction". Int. J. Hematol. 77 (1): 37–47. doi:10.1007/BF02982601. PMID 12568298.
- Tarkowski M (2004). "Expression and a role of CD30 in regulation of T-cell activity". Curr. Opin. Hematol. 10 (4): 267–71. doi:10.1097/00062752-200307000-00003. PMID 12799531.
- Granados S, Hwang ST (2004). "Roles for CD30 in the biology and treatment of CD30 lymphoproliferative diseases". J. Invest. Dermatol. 122 (6): 1345–7. doi:10.1111/j.0022-202X.2004.22616.x. PMID 15175022.
- Dürkop H, Latza U, Hummel M, et al. (1992). "Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease". Cell 68 (3): 421–7. doi:10.1016/0092-8674(92)90180-K. PMID 1310894.
- Fonatsch C, Latza U, Dürkop H, et al. (1992). "Assignment of the human CD30 (Ki-1) gene to 1p36". Genomics 14 (3): 825–6. doi:10.1016/S0888-7543(05)80203-4. PMID 1330892.
- Josimovic-Alasevic O, Dürkop H, Schwarting R, et al. (1989). "Ki-1 (CD30) antigen is released by Ki-1-positive tumor cells in vitro and in vivo. I. Partial characterization of soluble Ki-1 antigen and detection of the antigen in cell culture supernatants and in serum by an enzyme-linked immunosorbent assay". Eur. J. Immunol. 19 (1): 157–62. doi:10.1002/eji.1830190125. PMID 2537734.
- Stein H, Gerdes J, Schwab U, et al. (1983). "Identification of Hodgkin and Sternberg-reed cells as a unique cell type derived from a newly-detected small-cell population". Int. J. Cancer 30 (4): 445–59. doi:10.1002/ijc.2910300411. PMID 6754630.
- Jung W, Krueger S, Renner C, et al. (1995). "Opposite effects of the CD30 ligand are not due to CD30 mutations: results from cDNA cloning and sequence comparison of the CD30 antigen from different sources". Mol. Immunol. 31 (17): 1329–34. doi:10.1016/0161-5890(94)90051-5. PMID 7527901.
- Shiota M, Fujimoto J, Semba T, et al. (1994). "Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3". Oncogene 9 (6): 1567–74. PMID 8183550.
- Lee SY, Park CG, Choi Y (1996). "T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors". J. Exp. Med. 183 (2): 669–74. doi:10.1084/jem.183.2.669. PMC 2192463. PMID 8627180.
- Gedrich RW, Gilfillan MC, Duckett CS, et al. (1996). "CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins". J. Biol. Chem. 271 (22): 12852–8. doi:10.1074/jbc.271.22.12852. PMID 8662842.
- Horie R, Ito K, Tatewaki M, et al. (1996). "A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 by tetradecanoylphorbol acetate and is expressed in alveolar macrophages". Blood 88 (7): 2422–32. PMID 8839832.
- Aizawa S, Nakano H, Ishida T, et al. (1997). "Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation". J. Biol. Chem. 272 (4): 2042–5. doi:10.1074/jbc.272.4.2042. PMID 8999898.
- Lee SY, Lee SY, Choi Y (1997). "TRAF-interacting Protein (TRIP): A Novel Component of the Tumor Necrosis Factor Receptor (TNFR)- and CD30-TRAF Signaling Complexes That Inhibits TRAF2-mediated NF-κB Activation". J. Exp. Med. 185 (7): 1275–85. doi:10.1084/jem.185.7.1275. PMC 2196258. PMID 9104814.
- Boucher LM, Marengère LE, Lu Y, et al. (1997). "Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily". Biochem. Biophys. Res. Commun. 233 (3): 592–600. doi:10.1006/bbrc.1997.6509. PMID 9168896.
- Duckett CS, Thompson CB (1997). "CD30-dependent degradation of TRAF2: implications for negative regulation of TRAF signaling and the control of cell survival". Genes Dev. 11 (21): 2810–21. doi:10.1101/gad.11.21.2810. PMC 316646. PMID 9353251.
- Mizushima S, Fujita M, Ishida T, et al. (1998). "Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5)". Gene 207 (2): 135–40. doi:10.1016/S0378-1119(97)00616-1. PMID 9511754.
- Kurts C, Carbone FR, Krummel MF, et al. (1999). "Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells". Nature 398 (6725): 341–4. doi:10.1038/18692. PMID 10192335.
External links[edit]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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