Abstract 4380: LSR promotes cell proliferation and migration subsequent to uptake of fatty acid in epithelial ovarian cancer

Abstract

Abstract Background Previously, we identified lipolysis-stimulated lipoprotein receptor (LSR) as a new therapeutic target of epithelial ovarian cancer (EOC), and we reported anti-cancer effect of our newly developed monoclonal antibody (mAb) against LSR-positive EOC in vitro and in vivo. We also demonstrated that LSR took in triglyceride-rich protein and contributed cell proliferation, however, lipid metabolic pathway via LSR is still unclear. Thus, we aimed to reveal the function of LSR on lipid metabolism in EOC cells. Methods We investigated the activation of beta-oxidation, ATP production, cell proliferation and cell migration via LSR after administration of fatty acid (FA) using LSR-positive EOC cells and LSR-knockout EOC cells. Moreover, we also investigated anti-cancer effect of our anti-LSR mAb against lipid metabolism via LSR. Results In LSR-positive EOC cells, FA administration increased intracellular lipid accumulation. In glucose restricted environment, LSR promoted FA uptake and promoted ATP production (p < 0.05). In addition, FA promoted cell proliferation and cell migration in LSR-positive EOC cells (p < 0.05). These results suggest that LSR promoted FA uptake in glucose restricted environment and also promoted lipid metabolism including beta-oxidation, TCA cycle and electron transport system leading to ATP production. Finally, our anti-LSR mAb inhibited these lipid metabolic pathways (p < 0.05). Conclusions Fatty acid uptake via LSR in glucose restricted environment contributed to cell proliferation and migration subsequent to activation of lipid metabolism, and anti-LSR mAb inhibited these processes. LSR might contribute to cancer spread and metastasis of EOC. Citation Format: Kosuke Hiramatsu, Satoshi Serada, Minoru Fujimoto, Yutaka Ueda, Tadashi Kimura, Tetsuji Naka. LSR promotes cell proliferation and migration subsequent to uptake of fatty acid in epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4380.