Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype

Billy Samuel Hill, Alessandra Pelagalli, Nunzia Passaro and Antonella Zannetti _

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Oncotarget. 2017; 8:73296-73311. https://doi.org/10.18632/oncotarget.20265

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Billy Samuel Hill1,*, Alessandra Pelagalli1,2,*, Nunzia Passaro1 and Antonella Zannetti1

1Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Naples, Italy

2Department of Advanced Biomedical Sciences, University of Naples “Federico II”, Naples, Italy

*Authors contributed equally to this work

Correspondence to:

Antonella Zannetti, email: [email protected]

Keywords: mesenchymal stem cells, tumor microenvironment, epithelial-mesenchymal transition, metastatic phenotype

Received: February 03, 2017     Accepted: August 04, 2017     Published: August 14, 2017


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 cancer-associated 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.

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.

Furthermore, many studies report the use of MSCs engineered to express different genes or as vehicle to specifically deliver novel drugs to tumors exploiting their strong tropism. Importantly, this approach can enhance local therapeutic efficacy and reduce the risk of systemic side effects.

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