Analysis for an ovarian cancer-derived factor which decreases the expression of alpha-smooth muscle actin in stromal cells

点击翻译按钮获取中文摘要

We previously reported that both the conditioned mcdium (CM) of human ovarian cancer cell lines and the malignant ovarian tumor fluid reduced the expression of alpha-smooth muscle actin (alpha-SMA) in fibroblasts. ln this study, we confirmed the inhibitory effect existed in tumor fluid of malignant ovarian tumors but not that of benign ones by using a Western blot analysis. Ovarian cancer fluid-induced inhibition was partially blocked by a neutralizing antibody against platelet-devived growth factor (PDGF) in a dose-dependent fashion. On the other hand, the effect of benign ovarian tumor fluid was unchanged by adding the PDGF antibody. We next checked whether the CMs of human ovarian cancer cell lines contained PDGF or not by using an ELISA system. All of 9 epithelial originated cancer cell lines released PDGF into their culture media and one non-epithelial originated line did not. Although almost all of benign tumors did not contain PDGF in their tumor fluid, 80% of cancers contained relatively high levels of PDGF.Thus, PDGF released by ovarian cancer cells is thought to decrease the expression of alpha-SMA in surrounding stromal cells. alpha-SMA is a cytoskeletal protein expressed not only in stromal fibroblasts but also in the cells consisting in the vessel wall. If a decrease in alpha-SMA expression results in the enhancement of tumor cell invasion into stroma, it is possible that the cancer-derived PDGF,sis-oncogene product, has the role of enhancer of tumor invasion.