title: Mesenchymal Stem Cells Induce Directional Migration of Invasive Breast Cancer Cells through TGF-β.
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.
authors.affiliation: School of Chemical &Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: McAndrews
authors.affiliation: School of Chemical &Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McGrail
authors.affiliation: School of Chemical &Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Nithin
authors.initials: N
authors.lastname: Ravikumar
authors.affiliation: School of Chemical &Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.|The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Dawson
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D053505:Matrix Metalloproteinases, Secreted / Q000037:antagonists & inhibitors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D054460:rho-Associated Kinases; D053505:Matrix Metalloproteinases, Secreted