Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion

J Biol Chem. 2004 Mar 5;279(10):9190-8. doi: 10.1074/jbc.M312372200. Epub 2003 Dec 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA-125 Antigen / metabolism*
  • Cell Adhesion / physiology
  • Cell Line
  • Epithelium / metabolism
  • Epithelium / pathology
  • Female
  • GPI-Linked Proteins
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins
  • Mice
  • Neoplasm Metastasis
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Protein Binding

Substances

  • CA-125 Antigen
  • GPI-Linked Proteins
  • MUC16 protein, human
  • Membrane Glycoproteins
  • Membrane Proteins
  • mesothelin