Mesenchymal Stem Cells Induce Directional Migration of Invasive Breast Cancer Cells through TGF-β

Mesenchymal stem cells (MSCs) are recruited to the tumor microenvironment and influence tumor progression; however, how MSCs induce the invasion of cancer cells is not completely understood. Here, we used a 3D coculture model to determine how MSCs affect the migration of invasive breast cancer cells. Coculture with MSCs increases the elongation, directional migration, and traction generation of breast cancer cells. MSC-induced directional migration directly correlates with traction generation and is mediated by transforming growth factor beta (TGF-beta) and the migratory proteins rho-associated kinase, focal adhesion kinase, and matrix metalloproteinases. Treatment with MSC conditioned media or recombinant TGF-beta 1 elicits a similar migration response to coculture. Taken together, this work suggests TGF-beta is secreted by MSCs, leading to force-dependent directional migration of invasive breast cancer cells. These pathways may be potential targets for blocking cancer cell invasion and subsequent metastasis.