Journal
MOLECULAR CARCINOGENESIS
Volume 54, Issue 10, Pages 1214-1219Publisher
WILEY
DOI: 10.1002/mc.22178
Keywords
bone marrow mesenchymal stem cells; metastasis; TIMP-1; TIMP-2
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Funding
- Dean's Bequest Fund, Otago School of Medical Sciences, University of Otago
- University of Otago Research Grant
- Department of Pharmacology and Toxicology, University of Otago, New Zealand
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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-MB231 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. (C) 2014 Wiley Periodicals, Inc.
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