Carcinoma-associated fibroblasts (CAF) have recently been implicated in important aspects of epithelial solid
tumor biology, such as neoplastic progression,
tumor growth, angiogenesis, and
metastasis. However, neither the source of CAFs nor the differences between CAFs and fibroblasts from nonneoplastic tissue have been well defined. In this study, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) exposed to
tumor-
conditioned medium (TCM) over a prolonged period of time assume a CAF-like myofibroblastic phenotype. More importantly, these cells exhibit functional properties of CAFs, including sustained expression of stromal-derived factor-1 (SDF-1) and the ability to promote
tumor cell growth both in vitro and in an in vivo coimplantation model, and expression of myofibroblast markers, including alpha-smooth muscle actin and fibroblast
surface protein. hMSCs induced to differentiate to a myofibroblast-like phenotype using
5-azacytidine do not promote
tumor cell growth as efficiently as hMSCs cultured in TCM nor do they show increased SDF-1 expression. Furthermore, gene expression profiling revealed similarities between TCM-exposed hMSCs and CAFs. Taken together, these data suggest that hMSCs are a source of CAFs and can be used in the modeling of
tumor-stroma interactions. To our knowledge, this is the first report showing that hMSCs become activated and resemble
carcinoma-associated myofibroblasts on prolonged exposure to
conditioned medium from MDAMB231 human
breast cancer cells.