Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype

The development of novel therapeutic approaches targeting the different functions of MSCs in promoting tumor progression as well as the mechanisms underlying their activities could enhance the efficacy of conventional and immune anti-cancer therapies.

Multipotent mesenchymal stem cells (MSCs) are recruited into tumor microenvironment in response to multiple signals produced by cancer cells. Molecules involved in their homing to tumors are the same inflammatory mediators produced by injured tissues: chemokines, cytokines and growth factors. When MSCs arrive into the tumor microenvironment these are "educated"to have pro-metastatic behaviour. Firstly, they promote cancer immunosuppression modulating both innate and adaptive immune systems. Moreover, tumor associated-MSCs trans-differentiating into cancerassociated fibroblasts can induce epithelial-mesenchymal-transition program in tumor cells. This process determinates a more aggressive phenotype of cancer cells by increasing their motility and invasiveness and favoring their dissemination to distant sites. In addition, MSCs are involved in the formation and modelling of pre-metastatic niches creating a supportive environment for colonization of circulating tumor cells.