iprocal Activation of Prostate Cancer Cells and Cancer- ociated Fibroblasts Stimulates Epithelial-Mesenchymal

ownloade ough cancer-associated fibroblasts (CAF) are key determinants in the malignant progression of cancer, unctional contribution to this process is still unclear. Analysis of the mutual interplay between prostate oma cells and CAFs revealed a mandatory role of carcinoma-derived interleukin-6 in fibroblast activaturn, activated fibroblasts through secretion of metalloproteinases elicit in cancer cells a clear epithelialchymal transition (EMT), as well as enhancement of tumor growth and development of spontaneous tases. CAF-induced EMT leads prostate carcinoma cells to enhance expression of stem cell markers, as s the ability to form prostaspheres and to self-renew. Hence, the paracrine interplay between CAFs and well a cancer cells leads to an EMT-driven gain of cancer stem cell properties associated with aggressiveness and metastatic spread. Cancer Res; 70(17); 6945–56. ©2010 AACR.