Abstract TMEM-022: LYSOPHOSPHATIDIC ACID IN OVARIAN CANCER EPITHELIAL–TO–MESENCHYMAL TRANSITION

Abstract

Abstract Lysophosphatidic acid (LPA) is a bioactive phospholipid found in elevated concentrations in ovarian cancer (OVCA) patients. The objective of this study was to define the mechanism of action by which LPA contributes to ovarian carcinogenesis focusing on epithelial-to-mesenchymal transition (EMT) and role of human macrophages. THP-1 human macrophages and A27801AP human OVCA cells were used and treated with LPA up to 40 µM for 24 h. In THP-1 human macrophages, LPA treatment led to a dose-dependent increase in IL-1β secretion from 333.5 pg/mL (untreated) to 581.9, 661.8 and 1270.1 pg/mL for 10, 20 and 40 µM LPA treatment. We then used the conditioned medium (CM) from THP-1 macrophages to determine the effect on A27801AP OVCA cells. LPA-treated THP-1 CM increased the expression of EMT transcription factors p65, Slug and Snail as compared to non-LPA-treated THP-1 CM and resting OVCA cells. When A27801AP OVCA cells were treated with LPA alone, 20 µM LPA led to the same significant increase in the expression of EMT transcription factors p65, Slug and Snail. In addition, LPA treatment reduced the expression of the epithelial marker E-cadherin while increasing the expression of mesenchymal markers N-cadherin and vimentin which might be associated with increased phosphorylation of extracellular regulated kinase 1/2. The data show the role of LPA in modifying not only OVCA cells but also macrophages that can be found in the tumor microenvironment to promote progression of OVCA by promoting EMT. Citation Format: Vermont P Dia, Ph D. LYSOPHOSPHATIDIC ACID IN OVARIAN CANCER EPITHELIAL–TO–MESENCHYMAL TRANSITION [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-022.