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Tissue-Specific Stem Cells
Article first published online: 27 NOV 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 12, pages 2774–2783, December 2012
How to Cite
Strong, A. L., Semon, J. A., Strong, T. A., Santoke, T. T., Zhang, S., McFerrin, H. E., Gimble, J. M. and Bunnell, B. A. (2012), Obesity-Associated Dysregulation of Calpastatin and MMP-15 in Adipose-Derived Stromal Cells Results in their Enhanced Invasion. STEM CELLS, 30: 2774–2783. doi: 10.1002/stem.1229
Author contributions: A.L.S.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; J.A.S.: conception and design and data analysis and interpretation; T.A.S., T.T.S., and S.Z.: collection and assembly of data; H.E.M. and J.M.G.: conception and design, financial support, and data analysis and interpretation; B.A.B.: conception and design, financial support, data analysis and interpretation, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 7, 2012.
- Issue published online: 27 NOV 2012
- Article first published online: 27 NOV 2012
- Accepted manuscript online: 11 SEP 2012 01:56PM EST
- Manuscript Accepted: 21 AUG 2012
- Manuscript Received: 28 JUN 2012
- Tulane University (B.A.B.) and the Pennington Biomedical Research Center (J.M.G.)
- National Center for Research Resources. Grant Number: (5P20RR016456-11)
- National Institute of General Medical Sciences. Grant Number: (8 P20GM103424-11)
- National Institutes of Health
- Adipose-derived stromal/stem cell;
Adipose tissue maintains a subpopulation of cells, referred to as adipose-derived stromal/stem cells (ASCs), which have been associated with increased breast cancer tumorigenesis and metastasis. For ASCs to affect breast cancer cells, it is necessary to delineate how they mobilize and home to cancer cells, which requires mobilization and invasion through extracellular matrix barriers. In this study, ASCs were separated into four different categories based on the donor's obesity status and depot site of origin. ASCs isolated from the subcutaneous abdominal adipose tissue of obese patients (Ob+Ab+) demonstrated increased invasion through Matrigel as well as a chick chorioallantoic membrane, a type I collagen-rich extracellular matrix barrier. Detailed mRNA and protein analyses revealed that calpain-4, calpastatin, and MMP-15 were associated with increased invasion, and the silencing of each protease or protease inhibitor confirmed their role in ASC invasion. Thus, the data indicate that both the donor's obesity status and depot site of origin distinguishes the properties of subcutaneous-derived ASCs with respect to enhanced invasion and this is associated with the dysregulation of calpain-4, calpastatin, and MMP-15. STEM CELLS 2012;30:2774–2783