Tissue-resident stem cells promote breast cancer growth and metastasis.
Mesenchymal stem cells derived from bone marrow have recently been described to localize to breast carcinomas and to integrate into the tumor-associated stroma. In the present study, we investigated whether adipose tissue-derived stem cells (ASCs) could play a role in tumor growth and invasion. Compared with bone marrow-derived cells, ASCs as tissue-resident stem cells are locally adjacent to breast cancer cells and may interact with tumor cells directly. Here, we demonstrate that ASCs cause the cancer to grow significantly faster when added to a murine breast cancer 4T1 cell line. We further show that breast cancer cells enhance the secretion of stromal cell-derived factor-1 from ASCs, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. The tumor-promoting effect of ASCs was abolished by knockdown of the chemokine C-X-C receptor 4 in 4T1 tumor cells. We demonstrated that ASCs home to tumor site and promote tumor growth not only when co-injected locally but also when injected intravenously. Furthermore, we demonstrated that ASCs incorporate into tumor vessels and differentiate into endothelial cells. The tumor-promoting effect of tissue-resident stem cells was also tested and validated using a human breast cancer line MDA-MB-231 cells and human adipose tissue-derived stem cells. Our findings indicate that the interaction of local tissue-resident stem cells with tumor stem cells plays an important role in tumor growth and metastasis.
Muehlberg
Fabian L
FL
Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Song
Yao-Hua
YH
Krohn
Alexander
A
Pinilla
Severin P
SP
Droll
Lilly H
LH
Leng
Xiaohong
X
Seidensticker
Max
M
Ricke
Jens
J
Altman
Andrew M
AM
Devarajan
Eswaran
E
Liu
Weili
W
Arlinghaus
Ralph B
RB
Alt
Eckhard U
EU
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A