The objective of this study is to investigate interactions between adipocytes and breast cancer cells, and identify the responsible factors for the observed effects. In 27 breast cancer patients undergoing mastectomy, mammary adipose tissue was obtained from the breast quadrant bearing the tumor and corresponding non-tumoral quadrant. Isolated normal breast adipocytes (NBAs) and cancer-associated adipocytes (CAAs) were cultured in collagen gels to mimic the in vivo environment. Immunohistochemistry, qRT-PCR, and cell proliferation assays were performed to analyze adipocyte phenotypes. MCF7 and MDA-MB-231 breast cancer cell lines were co-cultured with adipocytes to detect phenotypic changes. Migration of MCF7 and MDA-MB-231 cells was assessed in NBA- and CAA-conditioned media. Cytokine levels in conditioned media were measured by cytokine array. Migration assays were repeated using conditioned media containing neutralizing antibodies. NBAs and CAAs lost their morphological phenotype in culture, acquiring a spindle-like shape, and CAAs showed higher cell proliferation, suggesting reversion to an immature phenotype. In co-cultures with MCF7 or MDA-MB-231 cells, NBAs exhibited increased cell proliferation, indicating acquisition of the immature phenotype of CAAs. MCF7 and MDA-MB-231 showed higher migration in a CAA-conditioned medium than in an NBA-conditioned medium. Cytokine array analysis of conditioned media revealed higher levels of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in the CAA-conditioned medium. Neutralization experiments using antibodies against IL-6 or MCP-1 showed abrogation of migration-enhancing effects of the CAA-conditioned medium. Adipocytes revert to an immature and proliferative phenotype in the presence of breast cancer cells, and promote cancer cell migration via adipokines including IL-6 and MCP-1.
Change in ADC after chemotherapy better correlated with pathological outcome and prognosis than change in tumor size. DWI has potential in evaluating the pathological outcome of NAC in breast cancer patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.