Implanted adipose progenitor cells as physicochemical regulators of breast cancer

被引:131
作者
Chandler, Emily M. [1 ]
Seo, Bo Ri [1 ]
Califano, Joseph P. [1 ]
Eguiluz, Roberto C. Andresen [2 ]
Lee, Jason S. [1 ]
Yoon, Christine J. [1 ]
Tims, David T. [1 ]
Wang, James X. [1 ]
Cheng, Le [3 ]
Mohanan, Sunish [3 ]
Buckley, Mark R. [4 ]
Cohen, Itai [4 ]
Nikitin, Alexander Yu [3 ]
Williams, Rebecca M. [1 ]
Gourdon, Delphine [2 ]
Reinhart-King, Cynthia A. [1 ]
Fischbach, Claudia [1 ]
机构
[1] Cornell Univ, Dept Biomed Engn, Ithaca, NY 14853 USA
[2] Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA
[3] Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA
[4] Cornell Univ, Dept Phys, Ithaca, NY 14853 USA
基金
美国国家科学基金会;
关键词
mechanobiology; desmoplasia; angiogenesis; tissue engineering; STEM-CELLS; DIFFERENTIATION; EXPRESSION; GROWTH; ELASTICITY; SCAFFOLDS; STROMA;
D O I
10.1073/pnas.1121160109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:9786 / 9791
页数:6
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