Mesenchymal stem cells enhance ovarian cancer cell infiltration through IL6 secretion in an amniochorionic membrane based 3D model

The early peritoneal invasion of epithelial ovarian cancer (EOC) by tumoral aggregates presents in ascites is a major concern. The role of the microenvironment seems to be important in this process but the lack of adequate models to study cellular interactions between cancer cells and stromal cells does not allow to uncover the molecular pathways involved. Our goal was to study the interactions between ovarian cancer cells (OCC) and mesenchymal stem cells (MSC) using a 3D model. We used millimetric pieces of amniochorionic membrane - referred to as amniotic membrane scaffold (AMS) - to create 3D peritoneal nodules mimicking EOC early invasion. We were able to measure the distribution and the depth of infiltration using confocal microsopy. We extracted MSC from the amniochorionic membrane using the markers CD34-, CD45-, CD73+, CD90+, CD105+ and CD29+ at the Fluorescence Activated Cell Sorting (FACS) analysis. We used transwell and wound healing tests to test OCC migration and invasion in vitro. Here we show that OCC tumors were located in regions rich in MSC (70%). The tumors infiltrated deeper within AMS in regions rich in MSC (p