CD157 expression enhances invasiveness of ovarian cancer cells and induces a mesenchymal phenotype

CD157 is a member of the nicotinamide adenine dinucleotide glycohydrolase (NADase)/adenosine diphosphate (ADP)-ribosyl cyclase gene family implicated in the control of myeloid cell adhesion, migration and diapedesis. Human CD157 is expressed by ~90 % of epithelial ovarian cancers and is a powerful independent predictive factor for disease recurrence and survival. We assessed the relevance of CD157 to migration and dissemination of ovarian cancer cells by transfecting the full-length cDNA in the poorly invasive, CD157-negative NIH:OVCAR-3 cell line. The results indicated that CD157 expression in NIH:OVCAR-3 cells is accompanied by marked morphological changes and enhanced spreading of cells. Moreover, CD157 expression reduces cell-cell aggregation and induces reorganization of the actin cytoskeleton thus promoting cell motility and invasiveness. Western blot analysis showed that CD157-positive cells are characterized by a significant decrease in E-cadherin and β-catenin expression compared to CD157-negative control cells. Taken together, these observations indicated that exogenous expression of CD157 is associated with the acquisition of morphological and molecular features of the mesenchymal-like phenotype. This was supported by the results of functional assays showing that CD157-positive NIH:OVCAR-3 cells are characterized by enhanced secretion of matrix metalloproteinase 2, 7 and 9, leading to an increased ability of tumor cells to remodel the extracellular matrix and invade the peritoneal mesothelium. The in vitro model of transmesothelial migration of ovarian cancer cells was reproduced deducing suitable Cellular Potts Models (CPM), a grid-based 3D multiscale mathematical model, which uses an hybrid approach to describe subcellular, cellular and tissue level interactions, combining cellular automata and continuum methods. Collectively, these results indicate that CD157 expression induces a mesenchymal phenotype resulting in increased cell invasiveness.