Binding of Ovarian Cancer Antigen CA125/MUC16 to Mesothelin Mediates Cell Adhesion
| Autor: | Masaki Takeuchi, Atsushi Miyajima, Armin Rump, Sawako Minami, Minoru Tanaka, Yoshihiro Morikawa, Naohiko Umesaki |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
endocrine system diseases
Immunoprecipitation Cell Amatuximab GPI-Linked Proteins Biochemistry Epithelium Cell Line Mice Ovarian carcinoma Cell Adhesion medicine Animals Humans Mesothelin Neoplasm Metastasis Cell adhesion Molecular Biology Ovarian Neoplasms Membrane Glycoproteins biology Membrane Proteins Cell Biology medicine.disease Molecular biology female genital diseases and pregnancy complications medicine.anatomical_structure CA-125 Antigen Expression cloning biology.protein Female Ovarian cancer Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 279:9190-9198 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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