The role of metallothionein genes in tumor-promoting effect of bone marrow-derived mesenchymal stem cells in human colon cancer

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To elucidate the role of bone marrow-derived mesenchymal stem cells (MSCs) on tumor growth and metastasis in human colon cancer, we performed microarray analysis of gene expression in KM12SM cells co-cultured with MSCs. Expression of metallothionein (MT) or fibronectin (FN) mRNA by KM12SM cells was increased markedly by indirect or direct co-culture with MSCs, respectively.We also examined MT and FN expression in surgical specimens of human colorectal neoplasms by immunohistochemistry. Expression of MT and FN in tumor cells was detected at the invasive edge. Furthermore, in an orthotopic nude mouse model of colon cancer, expression of FN was high in tumor nests near MSCs recruited in the tumor microenvironment, and expression of E-cadherin was decreased in tumor cells that expressed FN. These findings suggest MSCs recruited into tumor stroma may promote tumor growth and metastasis through induction of mesenchymal-epithelial transition in invasive colorectal cancers.