ESTRADIOL AND FIBULIN-1 INHIBIT MOTILITY OF HUMAN OVARIAN-CANCER AND BREAST-CANCER CELLS INDUCED BY FIBRONECTIN

Ovarian-cancer cells are characterized by their ability to invade free ly the peritoneal cavity. Estradiol stimulates the proliferation of es trogen-receptor(ER)-positive ovarian-cancer cells, as well as expressi on of fibulin-1, a fibronectin-binding extracellular matrix protein. U sing a modified Boyden-chamber assay, we have evaluated the respective roles of estradiol and fibulin-1 on cell motility, one of the earlier steps of tumor invasion. The effect of estradiol was examined on the random and directional migration of different ER-positive ovarian-canc er cell lines. The effect of fibulin-1 was studied on the motility of the MDA-MB231 breast-cancer cell line, which does not express fibulin- 1. We found that when fibronectin (FN) was used as an attractant, estr adiol decreased the cell motility of 2 ER-positive ovarian-cancer cell lines, BG-1 and SKOV3, but had no effect on 2 ER-negative cell lines, PEO14 and MDA-MB231. The inhibitory effect of estradiol was not obser ved when collagen (type 1 or 4) or laminin were used as attractants. F ibulin-1 was found to inhibit haptotactic migration of MDA-MB231 cells to FN in a dose-dependent manner. We conclude that both estradiol and fibulin-1 inhibit cancer cell motility in vitro and therefore have th e potential to inhibit tumor invasion. (C) 1998 Wiley-Liss, Inc.