Abstract 3320: Human bone marrow- and adipose-mesenchymal stem cells secrete inflammatory cytokines and growth factors in the presence of breast tumor cells

Introduction: Stem cell and adipocyte-epithelial interactions are mediated by tumor-enhancing factors such as cytokines, chemokines, and growth factors. The objective of our study was to identify novel secreted cytokines and growth factors common to mesenchymal stem cells and adipocytes and breast tumor cells using protein array analysis. Methods: Bone marrow (BM-MSC) or adipose (ASC) mesenchymal stem cells or their preadipocytes were co-cultured indirectly with MDA-MB-231 invasive breast cancer cells. Conditioned media was collected to compare protein expression levels using a cytokine antibody array. Signals were visualized, scanned, and quantitated by densitometry. Ingenuity Pathway Analysis mapped direct and indirect relationships between highly expressed proteins involved in obesity and the inflammation. Results: Within a week, stem cells derived from either bone marrow or adipose tissue differentiated into preadipocytes, as evident by staining with oil red O solution. Greater upregulation of cytokine and growth factor expression was observed when mesenchymal stem cells or preadipocytes were cultured in the presence of breast cancer cells. In BM-MSCs, IL-6, IL-6R, FGF9, ADIPOQ, and CXCL1 were the top five upregulated proteins, and IL13, IL2, CCL8, CXCL9, and TNF were the top five downregulated proteins when cultured with breast cancer cells. IL13, IL2, TNF, IL6, IL6R, and ADIPOQ are obesity-related while CXCL1, IL6, IL6R, ADIPOQ, CCL8, CXCL9, TNF, IL2, and IL13 are involved in inflammation. In ASCs, CXCL5, CCL5, IFNG, FGF7, and PDGF BB were the top five upregulated proteins, and CXCL11, ICAM3, IL6R, CCL16, and EGF were the top five downregulated proteins when cultured with breast cancer cells. CXCL11, IL6R, and CCL5 are obesity-related while IFNG, EGF, CCL16, IL6R, and CXCL11 are involved in the inflammatory response. IL7, CXCL3, ANG, CXCL11, and IGFBP1 were the top five upregulated proteins, and TNF, CCL18, IGFBP2, CCL15, and CCL20 were the top five downregulated proteins when BM-MSCs were differentiated into preadipocytes. CCL16, IL17, ICAM3, AGRP, and TNFSF18 were the top five upregulated proteins, and CCL3, IL6, FGF9, NAP1L4, and CSF1 were the top five downregulated proteins when ASCs were differentiated into preadipocytes. Conclusions: We identified a number of metabolic and inflammatory cytokines and growth factors common to bone and adipose tissue that could be involved in reciprocal communication between stem cells, their preadipocytes, and invasive breast cancer cells. A number of unique cytokines and growth factors were differentially expressed and under investigation for their roles in breast cancer. Citation Format: Brandi Talkington, Leah Figurski, Yuya Kudo, Kelsey Sadlek, Linda Vona-Davis. Human bone marrow- and adipose-mesenchymal stem cells secrete inflammatory cytokines and growth factors in the presence of breast tumor cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3320.