Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion.
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| Abstract |
Mesothelin is a glycosylphosphatidylinositol-linked cell surface molecule expressed in the mesothelial lining of the body cavities and in many tumor cells. Based on the finding that a soluble form of mesothelin specifically binds to ovarian carcinoma cell line OVCAR-3, we isolated cDNAs encoding a mesothelin-binding protein by expression cloning. The polypeptides encoded by the two cloned cDNA fragments matched to portions of CA125, an ovarian cancer antigen and a giant mucin-like glycoprotein present at the surface of tumor cells. By flow cytometric analysis and immunoprecipitation, we demonstrate that CA125 binds to mesothelin in a specific manner. Binding of CA125 to membrane-bound mesothelin mediates heterotypic cell adhesion as anti-mesothelin antibody blocks binding of OVCAR-3 cells expressing CA125 to an endothelial-like cell line expressing mesothelin. Finally, we show that CA125 and mesothelin are co-expressed in advanced grade ovarian adenocarcinoma. Taken together, our data indicate that mesothelin is a novel CA125-binding protein and that CA125 might contribute to the metastasis of ovarian cancer to the peritoneum by initiating cell attachment to the mesothelial epithelium via binding to mesothelin.
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| Authors | Armin Rump, Yoshihiro Morikawa, Minoru Tanaka, Sawako Minami, Naohiko Umesaki, Masaki Takeuchi, Atsushi Miyajima |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 10 Pg. 9190-8 (Mar 05 2004) ISSN: 0021-9258 [Print] United States |
| PMID | 14676194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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