Abstract 4487: Gene expression changes elicited by crosstalk between adipocytes and breast cancer cells

Abstract

Abstract Background: No longer considered simply an inert energy depot, adipose in the breast is increasingly recognized as an active endocrine tissue. Given the increasing rates of obesity in the US, choice of breast conserving surgery and use of autologous fat grafting, it is critical to understand how signals from adipocytes affect breast tumor cells and vice versa. Methods: Human subcutaneous preadipocytes were co-cultured for 3 days. Triple negative cell lines MDA-MB-231, SUM-149 and HCC-38 were then added and grown for a total of 10 days, with exposure to mature adipocytes for 7 days. Adipocytes and tumors cells were lysed from the plate and total RNA was isolated. Libraries were prepared for RNAseq and sequenced using a HiSeq2000. Differentially expressed genes were detected using the edge R package in R (v 3.3.3). Results: Co-culturing breast tumor cells demonstrated 110 differentially expressed genes compared to unexposed tumor cells including 6-fold lower expression of CLCA2 and 9-fold higher expression ZBTB16 in exposed tumor cells compared to controls. Pathway analysis demonstrated upregulation of 23 pathways such in the FoxO signaling and longevity regulating pathways and downregulation of tryptophan metabolism. In co-cultured adipocytes, 89 genes, including 9-fold higher expression of WNT7B and 13-fold lower expression of ADIPOQ. Pathways such as ECM-receptor interaction were upregulated and fat digestion and absorption were downregulated in co-cultured adipocytes. Conclusions: Exposure of adipocytes to tumor cells alters pathways involved in lipolysis and fatty acid metabolism in the adipocytes which may serve as a fuel source for tumor cells. In conjunction, exposure to adipocytes alters gene expression profiles in tumor cells associated with proliferation, migration and metastasis. These data demonstrate that proximity of breast tumor cells to adipocytes elicit significant gene expression changes in both cell types which synergistically promote tumorigenesis. The views expressed in this abstract are those of the author and do not reflect the official policy of the Department of Army, Navy, Air Force, Department of Defense, or U.S. Government. The identification of specific products, scientific instrumentation, or organization is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the author, DoD, or any component agency. Citation Format: Leann A. Lovejoy, Nicholas S. Costantino, Craig D. Shriver, Geogre Iida, Rachel E. Ellsworth. Gene expression changes elicited by crosstalk between adipocytes and breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4487.