Authors: Min Zhao, Patrick C. Sachs, Xu Wang, Catherine I. Dumur, Michael O. Idowu, Valentina Robila, Michael P. Francis, Joy Ware, Matthew Beckman, Aylin Rizki, Shawn E. Holt and Lynne W. Elmore

Min Zhao

Department of Pathology; Virginia Commonwealth University; Richmond, Virginia USA

Patrick C. Sachs

LifeNet Health; Regenerative Medicine Institute; Virginia Beach, VA USA

Xu Wang

Department of Pathology; Virginia Commonwealth University; Richmond, Virginia USA

Catherine I. Dumur

Department of Pathology; Virginia Commonwealth University; Richmond, Virginia USA; Massey Cancer Center; Virginia Commonwealth University; Richmond, Va Usa

Michael O. Idowu

Department of Pathology; Virginia Commonwealth University; Richmond, Virginia USA; Massey Cancer Center; Virginia Commonwealth University; Richmond, Virginia USA

Valentina Robila

Department of Pathology; Virginia Commonwealth University; Richmond, Virginia USA

Michael P. Francis

LifeNet Health; Regenerative Medicine Institute; Virginia Beach, VA USA

Joy Ware

Department of Pathology; Virginia Commonwealth University; Richmond, Virginia USA; Massey Cancer Center; Virginia Commonwealth University; Richmond, Virginia USA

Matthew Beckman

Deparment of Pharmacology and Toxicology; Virginia Commonwealth University; Richmond, Virginia USA

Aylin Rizki

Department of Radiation Oncology; Virginia Commonwealth University; Richmond, Virginia USA; Massey Cancer Center; Virginia Commonwealth University; Richmond, Virginia USA

Shawn E. Holt

Department of Pathology; Virginia Commonwealth University; Richmond, Virginia USA; Department of Human and Molecular Genetics; Virginia Commonwealth University; Richmond, Virginia USA; Deparment of Pharmacology and Toxicology; Virginia Commonwealth University; Richmond, Virginia USA; Massey Cancer Center; Virginia Commonwealth University; Richmond, Virginia USA; Department of Biology; Virginia State University; Petersburg, VA USA

Lynne W. Elmore

Corresponding author: lelmore@mcvh-vcu.edu
Department of Pathology; Virginia Commonwealth University; Richmond, Virginia USA; Massey Cancer Center; Virginia Commonwealth University; Richmond, Virginia USA; The School of Nursing Center for Biobehavioral Research; Virginia Commonwealth University; Richmond, Virginia USA

Abstract:
Data are accumulating to support a role for adipose-derived mesenchymal stem cells (MSCs) in breast cancer progression; however, to date most studies have relied on adipose MSCs from non-breast sources. There is a particular need to investigate the role of adipose MSCs in the pathogenesis of basal-like breast cancer, which develops at a disproportionate rate in pre-menopausal African-American women with a gain in adiposity. The aim of this study was to better understand how breast adipose MSCs (bMSCs) contribute to the progression of basal-like breast cancers by relying on isogenic HMT-3255 S3 (pre-invasive) and T4-2 (invasive) human cells that upon transplantation into nude mice resemble this tumor subtype. In vitro results suggested that bMSCs may contribute to breast cancer progression in multiple ways. bMSCs readily penetrate extracellular matrix components in part through their expression of matrix metalloproteinases 1 and 3, promote the invasion of T4-2 cells and efficiently chemoattract endothelial cells via a bFGF-independent, VEGF-A-dependent manner. As mixed xenografts, bMSCs stimulated the growth, invasion and desmoplasia of T4-2 tumors, yet these resident stem cells showed no observable effect on the progression of pre-invasive S3 cells. While bMSCs form vessel-like structures within Matrigel both in vitro and in vivo and chemoattract endothelial cells, there appeared to be no difference between T4-2/bMSC mixed xenografts and T4-2 xenografts with regard to intra- or peri-tumoral vascularity. Collectively, our data suggest that bMSCs may contribute to the progression of basal-like breast cancers by stimulating growth and invasion but not vasculogenesis or angiogenesis.

Received: February 13, 2012; Accepted: April 29, 2012; Published Online: June 6, 2012

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