Enhanced growth and metastasis of colon cancer: Role of mesenchymal stem cells

Abstract

Carcinoma-associated fibroblasts (CAFs) contribute to cancer progression, but their precise origin and role are unclear. Several studies have shown that bone marrow-derived mesenchymal stem cells (MSCs) migrate to tumor stroma and differentiate into CAFs in the specific tumor microenvironment. However, the actual role played by MSCs and the mechanisms underlying MSC-tumor interaction are only superficially understood. We recently studied the role of human MSCs in tumor stroma using an orthotopic nude mouse model of colon cancer. Circulating MSCs migrated not only to the stroma of primary colon tumors but also to metastatic liver tumors. Orthotopic transplantation of colon cancer cells mixed with MSCs, in comparison to transplantation of cancer cells alone, resulted in greater tumor weight and a greater number of liver metastases. Moreover, tumors resulting from transplantation of mixed cells had significantly higher cell proliferative and angiogenic activities as well as significantly fewer apoptotic tumor cells. Mesenchymal stem cells incorporated into the stroma of primary and metastatic tumors expressed CAF markers a -smooth muscle actin and platelet-derived growth factor receptor- b. Thus, MSCs migrate and differentiate into CAFs in tumor stroma, where they promote growth and metastasis of colon cancer by enhancing angiogenesis, migration, and invasion and by inhibiting apoptosis of tumor cells. Blockade of the tumor- MSC interaction may abrogate colon cancer progression.