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

Authors

  • Amy L. Strong,

    1. Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA
    Search for more papers by this author
  • Julie A. Semon,

    1. Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA
    Search for more papers by this author
  • Thomas A. Strong,

    1. Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA
    Search for more papers by this author
  • Tatyana T. Santoke,

    1. Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, USA
    Search for more papers by this author
  • Shijia Zhang,

    1. Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA
    2. Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA
    Search for more papers by this author
  • Harris E. McFerrin,

    1. Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA
    2. Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, USA
    Search for more papers by this author
  • Jeffrey M. Gimble,

    1. Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
    Search for more papers by this author
  • Bruce A. Bunnell

    Corresponding author
    1. Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA
    2. Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA
    • Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, SL-99, New Orleans, Louisiana 70112, USA
    Search for more papers by this author
    • Telephone: 504-988-7711; Fax: 504-988-7710


  • 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.

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. STEM CELLS 2012;30:2774–2783

Ancillary