Inhibition of Ovarian Cancer Chemoresistance and Metastasis with Antagonists of Hyaluronan-CD44-CD147 Interactions

Abstract

Abstract : The overall objective of our work on human ovarian carcinoma cells is to apply our previous molecular and cellular findings on the role of hyaluronan-CD44-CD147 interactions in cancer stem cell properties, especially drug resistance, to improvement of therapy for malignant ovarian carcinoma. In this grant we have shown that: a) drug-resistant human ovarian carcinoma cell lines contain CD133-positive/ CD147-positive/ CD44-positive cancer stem-like cells in similar proportion to that in human patient ascites-derived ovarian carcinoma cells, thus documenting their suitability for our studies; b) small hyaluronan oligosaccharides sensitize drug-resistant human ovarian carcinoma cells to various chemotherapeutic agents in culture and in vivo; c) CD147 silencing, via delivery of CD147 siRNA in liposomes, sensitizes cisplatin-resistant human ovarian carcinoma cells to cisplatin treatment in vivo; d) CD147 silencing decreases rates of metastases of human ovarian carcinoma cells in vivo. These results form the basis of promising new approaches to therapy in patients with recurrent, drug-resistant ovarian carcinoma.