Mesothelial cells induce the motility of human ovarian carcinoma cells

The dissemination of ovarian carcinoma cells within the abdominal cavity in volves interaction of tumor cells with the peritoneal mesothelium. The aim of our study was to investigate whether mesothelial cells might directly af fect the spreading of this tumor by inducing motility and invasiveness of h uman ovarian carcinoma cells. Serum-free supernatants of cultured human mes othelial cells [conditioned medium (CM)] induced chemotaxis and invasivenes s of the human ovarian carcinoma cell lines SK-OV-3, OVCAR-5 and A2780 in a Boyden chamber. Checkerboard analysis indicated that the stimulated motili ty was prevalently directional. Most of the chemotactic activity was retain ed by a heparin affinity column, indicating that the motility factor(s) is a heparin-binding protein. Using different monoclonal antibodies (MAbs) dir ected against chemotactic factors that are secreted by mesothelial cells, w e found that chemotaxis was partially prevented (64.8% inhibition) by antib odies against fibronectin (FN). CM also induced haptotactic migration of ov arian carcinoma cells, and anti-FN antibodies significantly inhibited hapto taxis. The presence of FN in the CM was confirmed by Western blot analysis. Our findings suggest that mesothelium plays an active role in inducing the intraperitoneal spread of ovarian carcinoma cells, and point to FN as bein g one of the main mediators of mesothelium-induced ovarian carcinoma cell m otility. (C) 1999 Wiley-Liss, Inc.