Title: Transforming growth factor beta enhances endometrial epithelial cell invasion by transforming growth factor beta receptor III signaling
Abstract: OBJECTIVE: To investigate the involvement of transforming growth factor beta receptor III (TGFBRIII) in transforming growth factor beta (TGF-β) enhancement of transmesothelial invasion in endometrial cells, an essential step in endometriotic lesion development. DESIGN: TGFBRIII deficient and control immortalized endometrial cells were introduced into a three dimensional in vitro system modeling the peritoneum with and without the addition of TGF-β. MATERIALS AND METHODS: Specific siRNA transfection was used to knockdown expression of TGFBRIII in EM 42 cells. Receptor expression was assessed with Real Time PCR and Western blot analysis. An established three dimensional in vitro system modeling the peritoneum was used for invasion assays. Differences were assessed by one-way ANOVA. RESULTS: TGF-β1 significantly increased invasion of control immortalized endometrial epithelial cells containing scrambled non-silencing siRNA through an in vitro transmesothelial membrane (p= 0.004). Invasion of TGFBRIII knockdown immortalized endometrial cells following treatment with TGF-β1 was significantly less than controls treated with TGF-β1 (p=0.004). CONCLUSION: TGFBRIII mediates TGF-β1 enhanced endometrial epithelial cell invasiveness by TGF-β. Combined with our previous studies showing that TGFBRI antagonists are potent inhibitors of TGF-β1 induced transmesothelial invasion, our data suggest that drugs targeting TGFBRIII pathways maybe useful in the treatment of endometriosis.