Induction of endometrial epithelial cell invasion and c-fms expression by transforming growth factor beta

Abstract

Transforming growth factor beta 1 (TGF-β1) levels are increased in the peritoneal fluid of endometriosis patients, and endometrial cells express TGF-β signaling components; however, little is known regarding the role of TGF-β in endometriosis. Our objective was to examine the effects of TGF-β1 on (i) the expression of macrophage colony-stimulating factor receptor encoded by the c-fms gene, (ii) transmesothelial invasiveness of endometrial cells, (iii) cellular proliferation and (iv) attachment to peritoneal mesothelial cells (PMCs). Effects of TGF-β1 on c-fms mRNA expression were determined by real-time RT-PCR and c-fms cell-surface expression by flow cytometry. Effects of TGF-β1 on the invasiveness of the immortalized endometrial epithelial cell (EEC) line EM42 and primary EECs were examined using a three-dimensional in vitro system modeling the peritoneum. Cellular proliferation and attachment to PMCs were also examined using established techniques. TGF-β1 had little or no effect on cellular proliferation and endometrial cell attachment to PMCs. TGF-β1 significantly induced the expression of c-fms mRNA and c-fms cell-surface expression. TGF-β1 enhanced transmesothelial invasion by EM42 cells and EECs. Antagonists of TGF-β1 signaling significantly inhibited both the induction of c-fms expression and cellular invasiveness, suggesting that additional studies are warranted to assess the therapeutic potential of TGF-β antagonists in endometriosis. © The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.