Implanted adipose progenitor cells as physicochemical regulators of breast cancer
| Autor: | Delphine Gourdon, Rebecca M. Williams, David T Tims, Jason Sang Hun Lee, Emily M. Chandler, Itai Cohen, Alexander Yu. Nikitin, Bo Ri Seo, Christine J Yoon, Sunish Mohanan, Joseph P. Califano, Roberto C. Andresen Eguiluz, James X Wang, Claudia Fischbach, Mark R. Buckley, Le Cheng, Cynthia A. Reinhart-King |
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| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty animal structures Cellular differentiation Adipose tissue Breast Neoplasms Biology medicine.disease_cause Regenerative medicine Extracellular matrix Mice Cell Line Tumor medicine Animals Humans Progenitor cell Multidisciplinary Cell Differentiation hemic and immune systems Biological Sciences eye diseases Extracellular Matrix Adipose Tissue Tumor progression Disease Progression Cancer research Female Stem cell Carcinogenesis Neoplasm Transplantation Stem Cell Transplantation |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:9786-9791 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1121160109 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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