Conditioned media from human ovarian cancer endothelial progenitor cells induces ovarian cancer cell migration by activating epithelial-to-mesenchymal transition

Bone marrow-derived endothelial progenitor cells (EPCs) migrate to and engraft at ovarian cancer sites. Understanding the interactions between ovarian cancer cells and EPCs is fundamental( for determining whether to harness EPC-tumor interactions for delivery Of therapeutic agents or target them for intervention. Ovarian Cancer cell lines (SKOV-3 and OVCAR-3) were cultured alone or in [PC-conditioned Media (EPC-CM). Migration of ovarian cancer cells was detected by transwell chamber. N-cadherin and E-cadherih expression were analyzed by real-time reverse transcription PO and western blot. EPC-CM can increase transforming growth factor-beta (TGF-beta) secretion in SKOV-3 and OVCAR3 cells. EPC-CM induced loss of ovarian cancer cell-cell junctions, downregulation of E-cadherin, Upregulation of N,cadherin and acquisition of a fibroblastic phenotype, consistent with an epithelial-to-Mesenchymal transition (EMT): The specific TGF-beta inhibitor SB431542 abolished the SKOV-3 and OVCAR-3 ovarian cancer cell migration induced by EPC-CM. In SKOV-3 and OVCAR-3 cells, EPC-CM downregulated E-cadherin and concurrently upregulated N-cadherin. EPC-CM upregulated the expression of transcriptional repressors of E-cadherin, Snail and Twist. Treatment with SB431542 abolished the effects Of EPC-CM on the relative expression levels of cadherin, Snail and Twist. This study demonstrates that TGF-beta has a role in EPC-CM-induced ovarian cancer migration by activating EMT.