Abstract B18: MiR-205 puts the brakes on the malignant interplay between prostate cancer cells and associated fibroblasts

Abstract

Abstract Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer associated fibroblasts (CAFs) elicit an epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, leading to enhanced tumor cell aggressiveness. Here, we investigated the involvement of microRNAs (miRNA) in such malignant tumor-stroma interplay, to identify possible tools to prevent metastasis dissemination. We found that miR-205 is the most down-modulated miRNA in PCa cells upon CAF stimulation and acknowledged HIF-1 to be a direct repressor of miRNA transcription. Rescue experiments demonstrated that ectopic miR-205 over-expression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity and metastatic dissemination. In addition, miR-205 can block tumor-driven activation of surrounding fibroblasts, by reducing pro-inflammatory cytokine secretion. Overall, these findings suggest a key role of miR-205 in the bidirectional interplay between PCa cells and fibroblasts. In addition, the evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert EMT induced by CAFs sets up the rationale for developing miRNA-based approaches for the prevention and treatment of aggressive tumors. Citation Format: Paolo Gandellini, Elisa Giannoni, Anna Casamichele, Maria Letizia Taddei, Maurizio Callari, Riccardo Valdagni, Nadia Zaffaroni, Paola Chiarugi. MiR-205 puts the brakes on the malignant interplay between prostate cancer cells and associated fibroblasts. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B18.