Tumor stroma consists of a complex microenvironment including extracellular matrix, growth factors, cytokines, and a variety of non-epithelial cells.Non-epithelial cells in tumor stroma are thought to be non-transformed, and include endothelial cells, immune cells, and fibroblasts.In many tumor types, fibroblasts comprise the major component of stroma, and play a significant role in the carcinogenic process.We hypothesized that the fibroblasts associated with ovarian cancer (OCAF) could promote the development of chemoresistance.OCAF were isolated and electronically sorted from ovarian cancer (OC) samples using flow cytometry.The contribution of OCAF and OCAF conditioned media (OCAF-CM) towards OC growth and apoptotic response to cisplatin was determined.Microarray gene expression data from 285 OC samples as well as 5 pairs of laser-capture microdissected samples of OC epithelial cells with matched samples of stromal cells from the same tumors was analyzed for differences in gene expression between stroma and ovarian carcinoma cells.Co-culturing OCAF or OCAF-CM with OC resulted in increased tumor cell growth and inhibition of cisplatin induced apoptosis.Furthermore, we found that multiple genes overexpressed in OC stroma as compared to epithelium are significantly associated with advanced, stage Ⅲ/Ⅳ disease.Our preliminary findings provide insight into OCAF signaling molecules, and suggest that the OC tumor microenvironment is a rich source of potential targets for future diagnostic or therapeutic intervention.