ESTROGENS INCREASE THE EXPRESSION OF FIBULIN-1, AN EXTRACELLULAR-MATRIX PROTEIN SECRETED BY HUMAN OVARIAN-CANCER CELLS

Ovarian cancers have a high ability to invade the peritoneal cavity an d some are stimulated by estrogens, In an attempt to understand the mo de of action of estrogens on these cancer cells and to develop new mar kers, we have characterized estrogen-regulated proteins, This study,va s aimed at identifying a protein secreted by ovarian cancer cells whos e level was increased by estradiol [Galtier-Dereure, F., Capony, F., M audelonde, T. & Rochefort, H. (1992) J. Clin. Endocrinol. Metab, 75, 1 197-1502]. By using microprotein sequencing, the 110-kDa protein was i dentified as fibulin-1, a protein of the extracellular matrix that bin ds to fibronectin, laminin, and nidogen, The amount of immunoprecipita ted fibulin-1 secreted into the medium and present in the cell extract was increased up to 10-fold by estradiol in three estrogen-responsive ovarian cancer cell lines. By immunohistochemistry fibulin-1 was loca ted in the stroma of several ovarian cancers and cysts. The findings h ighlight a potential role for fibulin-1 in the spread of ovarian cance r in the peritoneal cavity and/or in distal metastases.