ESTROGEN-RECEPTOR MEDIATED INHIBITION OF CANCER CELL INVASION AND MOTILITY - AN OVERVIEW

In this overview of results from our laboratory, we address the questi on of the role of estrogens during early steps of metastasis, involvin g cell invasion through the basement membrane and cell motility. The m otility of several estrogen receptor (ER) positive breast (MCF7, T47D) and ovarian (BG-1, SKOV3, PEO4) cancer cell lines was studied using a modified Boyden chamber assay. We observed, in all cases, estradiol i nduced inhibition of cancer cell invasion and motility. A similar inhi bitory effect of estradiol was found when the wild-type ER alpha was s tably transfected in the ER-negative MDA-MB231 cells and 3Y1-Ad12 canc er cells. The mechanism of this inhibitory effect is unknown. In ovari an cancer, however, it may involve intermediary proteins such as fibul in-1, an extracellular matrix protein that strongly interacts with fib ronectin and which is induced by estrogen and secreted by ovarian canc er cells. We conclude that estrogens in ER-positive breast and ovarian cancers have a dual effect, since they stimulate tumor growth but inh ibit invasion and motility. This may be consistent with the good initi al prognostic value of ER-positive breast cancers compared to ER negat ive breast cancers noted in several clinical studies. (C) 1998 Elsevie r Science Ltd. All rights reserved.