Implanted adipose progenitor cells as physicochemical regulators of breast cancer.
Chandler EM, Seo BR, Califano JP, Andresen Eguiluz RC, Lee JS, Yoon CJ, Tims DT, Wang JX, Cheng L, Mohanan S, Buckley MR, Cohen I, Nikitin AY, Williams RM, Gourdon D, Reinhart-King CA, Fischbach C.
Proc Natl Acad Sci USA
Cells used in publication:
Endothelial, umbilical vein, human (HUVEC)
Tissue Origin: vein
Adipose stem cell, human normal
Tissue Origin: adipose
Endothelial Cell Growth Medium 2
Adipose-derived Stem Cell Growth Medium
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.
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