Abstract B007: Stemness features of prostate cancer cells induced by carcinoma-associated fibroblasts

Abstract

Abstract Introduction: Carcinoma-associated fibroblasts (CAFs) play a key role during cancer progression through several mechanisms, including the induction of the epithelial-mesenchymal transition (EMT) program, giving cancer cells the ability to initiate metastasis. As the cells progress to the mesenchymal state they acquire properties of cancer stem cells (CSC) or mesenchymal stem cell (MSC). However, the contribution of the CAFs in the acquisition of the differential stemness is largely unknown. Here, we studied the stemness features of prostate cancer cells (PC3) during the EMT program induced by fibroblasts obtained from patients with nonmetastatic prostate cancer (CAF) and bone metastatic prostate cancer (mCAF). Materials and Methods: PC3 cells were incubated with conditioned medium (CM) of CAF and mCAF for 7,14, and 21 days to induced EMT. The presence of putative CSCs and MSCs was determined by qPCR, immunocytochemistry and Western blot for the expression of CSCs and MSCs markers, respectively, and functionally evaluated by the ability to perform adipogenic, chondrogrenic, and osteogenic differentiation (MSCs) and in vitro spheroids formation and clonogenic assay (CSCs). Results and Discussion: Our results demonstrate that cancer cells treated with CM-CAF undergo to a partial EMT program, exhibiting certain mesenchymal traits and enriched for cancer stem cells (CSCs). On the other hand, tumor cells exposed to CM-mCAF, exhibited a full EMT conversion with the greater abilities to migrate and invade in vitro and in vivo. This suggests that CAFs and mCAFs induce differential EMT programs in prostate cancer cells, which leads them to acquire CSCs or MSC features enhancing the metastatic capabilities. (FONDECYT 1150397.) Citation Format: Muriel A. Nuñez, Javier Cerda-Infante, Marianela Sánchez, Paula Sotomayor, Alejandro S. Godoy, Viviana P. Montecinos. Stemness features of prostate cancer cells induced by carcinoma-associated fibroblasts [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B007.