Mesenchymal stem cells in mammary adipose tissue stimulate progression of breast cancer resembling the basal-type.
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.
Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, USA.
Min
M
Zhao
Patrick C
PC
Sachs
Xu
X
Wang
Catherine I
CI
Dumur
Michael O
MO
Idowu
Valentina
V
Robila
Michael P
MP
Francis
Joy
J
Ware
Matthew
M
Beckman
Aylin
A
Rizki
Shawn E
SE
Holt
Lynne W
LW
Elmore
D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology*; D045744:Cell Line, Tumor; D002633:Chemotaxis; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D042361:Mammary Glands, Human / Q000473:pathology*; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D018295:Neoplasms, Basal Cell / Q000098:blood supply / Q000473:pathology*; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015703:Antigens, CD; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D053505:Matrix Metalloproteinases, Secreted