Abstract
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 β (TGF-β) and the migratory proteins rho-associated kinase, focal adhesion kinase, and matrix metalloproteinases. Treatment with MSC conditioned media or recombinant TGF-β1 elicits a similar migration response to coculture. Taken together, this work suggests TGF-β 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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Breast Neoplasms / metabolism
-
Breast Neoplasms / pathology
-
Cell Culture Techniques / methods*
-
Cell Line, Tumor
-
Cell Movement / drug effects
-
Cell Movement / physiology*
-
Cells, Cultured
-
Coculture Techniques
-
Culture Media, Conditioned / pharmacology
-
Enzyme Inhibitors / pharmacology
-
Female
-
Focal Adhesion Kinase 1 / antagonists & inhibitors
-
Focal Adhesion Kinase 1 / metabolism
-
Humans
-
MCF-7 Cells
-
Matrix Metalloproteinases, Secreted / antagonists & inhibitors
-
Matrix Metalloproteinases, Secreted / metabolism
-
Mesenchymal Stem Cells / cytology*
-
Mesenchymal Stem Cells / metabolism
-
Microscopy, Fluorescence
-
Neoplasm Invasiveness
-
Receptors, Transforming Growth Factor beta / antagonists & inhibitors
-
Receptors, Transforming Growth Factor beta / metabolism
-
Transforming Growth Factor beta / metabolism*
-
Transforming Growth Factor beta / pharmacology
-
rho-Associated Kinases / antagonists & inhibitors
-
rho-Associated Kinases / metabolism
Substances
-
Culture Media, Conditioned
-
Enzyme Inhibitors
-
Receptors, Transforming Growth Factor beta
-
Transforming Growth Factor beta
-
Focal Adhesion Kinase 1
-
PTK2 protein, human
-
rho-Associated Kinases
-
Matrix Metalloproteinases, Secreted