Abstract
Tumor progression depends on the tumor-stroma interaction. In the breast, adipose tissue is the predominant stromal type. We have previously demonstrated that conditioned media (CMs) from explants of human adipose tissue of tumor breasts (hATT) increase proliferation and migration of breast cancer epithelial cells when compared to human adipose tissue from normal breasts (hATN). In this work, we aim to identify specific proteins and molecular/biological pathways associated with the secretion profile of hATT and hATN explants.hATT-CMs and hATN-CMs were separated by SDS-PAGE and analyzed by means of two-dimensional nano-liquid chromatography-mass spectrometry. The data was analyzed using ProteoIQ and FunRich software. In addition, 42 cytokines from hATT-CMs and hATN-CMs were assayed by a protein antibody assay. Compared to hATN-CMs, hATT-CMs showed greater protein diversity. We found that hATT-CMs presented a greater amount of proteins related to complement system activity, metabolism and immune system, as well as proteins involved in a variety of biological processes such as signal transduction and cell communication. Specifically, apolipoprotein AI and AII, complement component 3, and vimentin and desmin were significantly increased in hATT-CMs versus hATN-CMs. Moreover, a multivariate discriminant analysis of the cytokines detected by the array showed that IL-6, MCP-2 and GRO cytokines were sufficient and necessary to differentiate hATT-CMs from hATN-CMs. This analysis also showed that the levels of these three cytokines, taken together, correlated with stage and histological grade of the tumor in the hATT-CMs group, and with body mass index in the hATN-CMs group.
Highlights
RESULTSAn essential information exchange is established between epithelial tissue and fibroblastic/adipose stroma during normal morphogenesis and functionality of the breast, as well as in cancer development
We have previously demonstrated that conditioned media (CMs) from explants of human adipose tissue of tumor breasts increase proliferation and migration of breast cancer epithelial cells when compared to human adipose tissue from normal breasts
We have recently shown that conditioned media (CMs) from explants of human adipose tissue from tumor breasts increase the proliferation and migration of breast cancer epithelial cell lines, as opposed to CMs from explants of adipose tissue from normal breasts [17]
Summary
RESULTSAn essential information exchange is established between epithelial tissue and fibroblastic/adipose stroma during normal morphogenesis and functionality of the breast, as well as in cancer development. Some groups have studied the secretome from tumor breast adipose tissue and interstitial fluid from fresh adipose tissue from cancer patients [19, 20]. In both cases, the breast adipose tissue was only from a tumor microenvironment origin. We aim to characterize proteins and molecular/biological processes and pathways associated with differences between CMs of human adipose tissue from normal (hATN) and tumor (hATT) breasts. To our knowledge, the first proteomic analysis which compares breast adipose tissue from healthy women with that of a tumor microenvironment from cancer patients
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