Abstract P4-03-15: Joint influence by paracrine adipocyte signals and metabolic conditions on breast cancer

Abstract

Abstract Background: The growing global population of overweight and obese people represents a pressing public health concern. A higher percentage of body fat is linked to an altered metabolic state and an increased risk of chronic metabolic disorders and cancer. Although, the mechanistic explanations for how obesity affects the development, progression and prognosis of cancer is incompletely mapped. Purpose: To investigate the joint influence by adipocytes and metabolic pressure on breast cancer cell expansion. Experimental Design: In vitro differentiated 3T3-L1 adipocytes were exposed to metabolic glucoselow/high and insulinlow/high pressure in order to mimic normal, pre-diabetic, overt diabetic and late diabetic conditions. Adipocyte-conditioned medium was collected and paracrine effects by adipocyte-derived factors on estrogen receptor (ER)-positive (T47D, MCF-7) and ER-negative (MDA-MB-231) breast cancer cell proliferation, molecular adaptations, and cell motility were subsequently analyzed using sulforhodamine B, Western immunoblotting and migration assays. Results: Under normal metabolic conditions, adipocytes stimulated the growth of ER+ (1.1-2.0-fold; P<0.001) and to a greater extent, ER- breast cancer cells (3.1-fold; P<0.001), compared with controls. The joint effects by adipocyte paracrine signals and higher metabolic pressure (overt or late diabetic conditions), further enhanced the proliferative response in both ER+ and ER- cells (1.3-3.5-fold; P<0.01), compared with controls. Furthermore, adipocyte-derived factors induced morphological changes, protrusion extensions and cell migration in the low invasive T47D cells. Additional acquisition of molecular epithelial-mesenchymal transition features were observed in breast cancer cells following co-culturing with adipocyte-derived factors. Conclusion: These study results support the hypothesis that paracrine signals by adipocytes significantly stimulate the proliferation and induction of a more motile phenotype of human breast cancer cells, which is further enhanced under obesity-associated metabolic conditions. Citation Format: Rosendahl AH, Bergqvist M, Lettiero B, Kimbung S, Borgquist S. Joint influence by paracrine adipocyte signals and metabolic conditions on breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-15.