title: Mesenchymal stem cells inhibit breast cancer cell migration and invasion through secretion of tissue inhibitor of metalloproteinase-1 and -2.
abstract: Mesenchymal stem cells (MSCs) form part of tumor stroma, and are typically considered to be pro-tumorigenic, promoting continuing tumor growth and metastasis. Here, we describe a mechanism by which MSCs may be anti-tumorigenic, through inhibition of breast cancer cell migration and invasion, an important part of metastasis. MDA-MB-231 and T47D cells were co-cultured in a Transwell insert above MSCs or MSC conditioned media and their migration or invasion through Matrigel measured. The conditioned media was found to inhibit breast cancer cell movement. TIMP-1 and TIMP-2, inhibitors of matrix metalloproteinases (MMPs), were identified as candidates for this inhibition and enhanced secretion of MMPs was not sufficient to counter the anti-migratory effects of TIMP expression. Inhibition of TIMP activity showed that TIMP-1 and TIMP-2 together were largely responsible for the reduction of migration and invasion by MSCs. Therefore, MSCs may play anti-tumorigenic, anti-metastatic roles in tumor development, with the overall outcome dependent upon the balance of pro-and anti-tumorigenic molecules secreted.
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Clarke
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Floriane M
authors.initials: FM
authors.lastname: Imhoff
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Baird
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018920:Coculture Techniques / Q000379:methods; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C059485:matrigel; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen
keywords: TIMP-1; TIMP-2; bone marrow mesenchymal stem cells; metastasis