Implanted adipose progenitor cells as physicochemical regulators of breast cancer.
Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer.
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Emily M
EM
Chandler
Bo Ri
BR
Seo
Joseph P
JP
Califano
Roberto C
RC
Andresen Eguiluz
Jason S
JS
Lee
Christine J
CJ
Yoon
David T
DT
Tims
James X
JX
Wang
Le
L
Cheng
Sunish
S
Mohanan
Mark R
MR
Buckley
Itai
I
Cohen
Alexander Yu
AY
Nikitin
Rebecca M
RM
Williams
Delphine
D
Gourdon
Cynthia A
CA
Reinhart-King
Claudia
C
Fischbach
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018450:Disease Progression; D005109:Extracellular Matrix; D005260:Female; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D033581:Stem Cell Transplantation