Tissue factor pathway inhibitor-2 (TFPI2) is a Kunitz-type serine protease inhibitor and an ovarian clear cell carcinoma (CCC) biomarker. TFPI2 is expressed in several cancers and exerts tumor-suppressive effects; however, the role of TFPI2 in the CCC cell phenotype remains unclear. Therefore, in this study, we investigated the function of TFPI2 by establishing a gene knockout (KO) in ES-2 CCC cells and observed the change in phenotypes in vitro and in vivo. TFPI2 KO inhibited ES-2 cell proliferation, increased extracellular matrix protein adhesion, enhanced focal adhesion formation and activated integrin β1 cell surface clustering in vitro, and markedly increased ES-2 tumor growth and dissemination in the peritoneal cavity of a mouse xenograft model. These findings suggest a novel function of TFPI2 expression in suppressing the formation of focal adhesions in CCC cells, potentially by activating integrin β1. This function plays a role in the peritoneal growth characteristics of CCC cells.
Keywords: Dissemination; Focal adhesion; Integrin β1; Ovarian cancer; Tissue factor pathway inhibitor-2.
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