To grab the stroma by the horns: From biology to cancer therapy with mesenchymal stem cells

// Ilia A. Droujinine 1 , Mark A. Eckert 2 and Weian Zhao 2 1 Department of Genetics, Harvard Medical School, Boston, MA 2 Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Department of Biomedical Engineering, and Department of Pharmaceutical Sciences, University of California, Irvine, CA Correspondence: Weian Zhao, email: // Keywords : mesenchymal stem cells, cell therapy, stroma, microenvironment, tumor associated fibroblasts Received : May 17, 2013 Accepted : May 28, 2013 Published : May 31, 2013 Abstract Mesenchymal stem or stromal cells (MSCs) are precursor cells that play important roles in tumorigenesis. MSCs are recruited to tumors from local and distant sources to form part of the tumor microenvironment. MSCs influence tumor progression by interacting with cancer cells, endothelial cells, immune cells, and cancer stem cells, in a context-dependent network. This review aims to synthesize this emerging yet controversial field to identify key questions regarding the mechanisms of MSC mobilization and survival in blood; homing to tumors, metastases, and premetastatic sites; spatiotemporal organization and differentiation; and interaction with immune cells and cancer stem cells.Understanding the fundamental biology underlying mesenchymal stem cell and tumor interactions has the potential to inform our knowledge of cancer initiation and progression as well as lead to novel therapeutics for cancer. Furthermore, knowledge of endogenous mechanisms can be used to “program” exogenous MSCs for targeted chemotherapeutic delivery to tumors and metastases. Emerging studies will provide crucial insight into the mechanisms of tumor interactions with the whole organism including MSCs.