Mesothelin
Mesothelin also known as MSLN is a protein that in humans is encoded by the MSLN gene.[1][2]
Function
Mesothelin is a 40kDa protein present on normal mesothelial cells and overexpressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. The protein was first identified by its reactivity with monoclonal antibody K1.[3] 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.[4]
Therapeutic application
Mesothelin is a tumour differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium.[5] 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.[4][5]
References
- ^ 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. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=7665620.
- ^ 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. doi:10.1073/pnas.93.1.136. PMC 40193. PMID 8552591. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=8552591.
- ^ 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 Res 52 (1): 181–6. PMID 1727378.
- ^ a b Hassan R, Bera T, Pastan I (June 2004). "Mesothelin: a new target for immunotherapy". Clin. Cancer Res. 10 (12 Pt 1): 3937–42. doi:10.1158/1078-0432.CCR-03-0801. PMID 15217923.
- ^ 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 2265108. PMID 17945478. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2265108.
Further reading
- Alvarez H, Rojas PL, Yong KT, et al. (2008). "Mesothelin is a specific biomarker of invasive cancer in the Barrett-associated adenocarcinoma progression model Translational implications for diagnosis and therapy". Nanomedicine : nanotechnology, biology, and medicine 4 (4): 295–301. doi:10.1016/j.nano.2008.06.006. PMC 2606904. PMID 18691948. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2606904.
- Cristaudo A, Foddis R, Bonotti A, et al. (2009). "Polymorphisms within the putative micro-RNA binding sites of mesothelin gene are associated with the serum levels of the mesothelin-related protein". Occup Environ Med 67 (4): 233–6. doi:10.1136/oem.2009.049205. PMID 19858537.
- Pu RT, Pang Y, Michael CW (2008). "Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions". Diagn. Cytopathol. 36 (1): 20–5. doi:10.1002/dc.20747. PMID 18064689.
- Inami K, Kajino K, Abe M, et al. (2008). "Secretion of N-ERC/mesothelin and expression of C-ERC/mesothelin in human pancreatic ductal carcinoma". Oncol. Rep. 20 (6): 1375–80. PMID 19020717.
- Roe OD, Creaney J, Lundgren S, et al. (2008). "Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study". Lung Cancer 61 (2): 235–43. doi:10.1016/j.lungcan.2007.12.025. PMID 18281122.
- Johnson MD, Vito F, O'Connell MJ (2008). "Mesothelin Expression in the Leptomeninges and Meningiomas". J. Histochem. Cytochem. 56 (6): 579–85. doi:10.1369/jhc.2008.950477. PMC 2386771. PMID 18347077. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2386771.
- Schneider J, Hoffmann H, Dienemann H, et al. (2008). "Diagnostic and prognostic value of soluble mesothelin-related proteins in patients with malignant pleural mesothelioma in comparison with benign asbestosis and lung cancer". J Thorac Oncol 3 (11): 1317–24. doi:10.1097/JTO.0b013e318187491c. PMID 18978568.
- Pass HI, Wali A, Tang N, et al. (2008). "Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions". Ann. Thorac. Surg. 85 (1): 265–72; discussion 272. doi:10.1016/j.athoracsur.2007.07.042. PMID 18154821.
- Sapede C, Gauvrit A, Barbieux I, et al. (2008). "Aberrant splicing and protease involvement in mesothelin release from epithelioid mesothelioma cells". Cancer Sci. 99 (3): 590–4. doi:10.1111/j.1349-7006.2007.00715.x. PMID 18167128.
- Li M, Bharadwaj U, Zhang R, et al. (2008). "Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer". Mol. Cancer Ther. 7 (2): 286–96. doi:10.1158/1535-7163.MCT-07-0483. PMC 2929838. PMID 18281514. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2929838.
- Uehara N, Matsuoka Y, Tsubura A (2008). "Mesothelin promotes anchorage-independent growth and prevents anoikis via extracellular signal-regulated kinase signaling pathway in human breast cancer cells". Mol. Cancer Res. 6 (2): 186–93. doi:10.1158/1541-7786.MCR-07-0254. PMID 18245228.
- Iwahori K, Osaki T, Serada S, et al. (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.
- Creaney J, Yeoman D, Demelker Y, et al. (2008). "Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma". J Thorac Oncol 3 (8): 851–7. doi:10.1097/JTO.0b013e318180477b. PMID 18670302.
- Shiomi K, Hagiwara Y, Sonoue K, et al. (2008). "Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma". Clin. Cancer Res. 14 (5): 1431–7. doi:10.1158/1078-0432.CCR-07-1613. PMID 18316566.
- Kaneko O, Gong L, Zhang J, et al. (2009). "A Binding Domain on Mesothelin for CA125/MUC16". J. Biol. Chem. 284 (6): 3739–49. doi:10.1074/jbc.M806776200. PMC 2635045. PMID 19075018. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2635045.
- Chang MC, Chen CA, Hsieh CY, et al. (2009). "Mesothelin inhibits paclitaxel-induced apoptosis through the PI3K pathway". Biochem. J. 424 (3): 449–58. doi:10.1042/BJ20082196. PMID 19747165.
- Cheng WF, Huang CY, Chang MC, et al. (2009). "High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma". Br. J. Cancer 100 (7): 1144–53. doi:10.1038/sj.bjc.6604964. PMC 2669998. PMID 19293794. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2669998.
- Hellstrom I, Hellstrom KE (2008). "SMRP and HE4 as biomarkers for ovarian carcinoma when used alone and in combination with CA125 and/or each other". Adv. Exp. Med. Biol.. Advances in Experimental Medicine and Biology 622: 15–21. doi:10.1007/978-0-387-68969-2_2. ISBN 978-0-387-68966-1. PMID 18546615.
- Bharadwaj U, Li M, Chen C, Yao Q (2008). "Mesothelin-Induced Pancreatic Cancer Cell Proliferation Involves Alteration of Cyclin E via Activation of Stat3". Mol. Cancer Res. 6 (11): 1755–65. doi:10.1158/1541-7786.MCR-08-0095. PMC 2929833. PMID 19010822. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2929833.