Tumor microenvironment: bone marrow-mesenchymal stem cells as key players

Tumor progression is a multistep phenomenon in which tumor-associated stromal cells perform an intricate cross-talk with tumor cells, supplying appropriate signals that may promote tumor aggressiveness. Among several cell types that constitute the tumor stroma, the discovery that bone marrow-derived mesenchymal stem cells (BM-MSC) have a strong tropism for tumors has achieved notoriety in recent years. Not only are the BM-MSC recruited, but they can also engraft at tumor sites and transdifferentiate into cells such as activated fibroblasts, perivascular cells and macrophages, which will perform a key role in tumor progression. Whether the BM-MSC and their derived cells promote or suppress the tumor progression is a controversial issue. Recently, it has been proposed that proinflammatory stimuli can be decisive in driving BM-MSC polarization into cells with either tumor-supportive or tumor-repressive phenotypes (MSC1/MSC2). These considerations are extremely important both to an understanding of tumor biology and to the putative use of BM-MSC as "magic bullets" against tumors. In this review, we discuss the role of BM-MSC in many steps in tumor progression, focusing on the factors that attract BM-MSC to tumors, BM-MSC differentiation ability, the role of BM-MSC in tumor support or inhibition, the immunomodulation promoted by BM-MSC and metastatic niche formation by these cells.