Obesity-Associated Dysregulation of Calpastatin and MMP-15 in Adipose-Derived Stromal Cells Results in Their Enhanced Invasion

Abstract

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.

Department(s)

Biological Sciences

Keywords and Phrases

Adipose-derived stromal/stem cell; Calpastatin; Cancer; Invasion; MMP-15; Obesity

International Standard Serial Number (ISSN)

1066-5099

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2012 AlphaMed Press, All rights reserved.

Publication Date

01 Dec 2012

PubMed ID

22969001

Link to Full Text

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