Abstract 2501: Involvement of Notch signaling pathway in a panel of human cancer cell lines

Abstract

Abstract Background. Notch pathway has been involved in cell fate determination, cell differentiation, cell proliferation, apoptosis, angiogenesis and drug resistance, as well as epithelial-to-mesenchymal transition (EMT). Our team has demonstrated the involvement of the PlGF/VEGFR1/Notch4 axis in the angiogenesis of HCC, but what about the role of Notch in cancer cells? In this study, we will focus on Notch1 and Notch4 since they have been extensively described in tumor angiogenesis. The aim of this work is to characterize the expression and the role of basal Notch1 and Notch4 activation in a panel of human cancer cell lines. Materials and Methods. We characterized a panel of 8 pancreatic, 5 cholangiocarcinoma (CK), 5 colorectal, 8 head and neck (H&N), and 5 hepatocellular (HCC) human cancer cell lines for Notch1, Notch4, E-cadherin, and Vimentin expressions by Western Blot. In each cancer type, 2 cell lines were chosen (one each with high and low Notch expression, respectively) to further assess the role of Notch basal expression in cellular properties such as migration, invasion, and vasculogenic mimicry, by using wound-healing test, Boyden chamber assay, and Ibidi plates, respectively. We also studied the effects of Notch inhibition on those cellular activities. Results. Our first results showed that Notch1 and Notch4 are activated in most of cancer cell lines at basal state. Notch4 is highly activated in 6 out of 8 pancreas cell lines, 7 out of 8 H&N cell lines, 2 out of 3 HCC cell lines, 3 out of 5 CK cell lines, and 2 out of 5 colon cell lines. In contrast, Notch1 is activated in all the CK cells, 3 out of 8 H&N cell lines, and 2 out of 3 HCC cell lines. Interestingly, in pancreatic and HCC cell lines, Notch4 activation is correlated with high expression of Vimentin. These results raised the question of the implication of Notch basal activation in the aggressiveness of tumor cells. Thus, we will further investigate the role of Notch1 and Notch4 in migration and invasion properties of tumor cells. Furthermore, since Notch1 and Notch4 are widely described in angiogenesis, we will also assess the vasculogenic mimicry properties of tumor cell with high versus low basal activation of Notch1 and Notch4. These results will be displayed at the conference. Conclusions. In this study, we show the high prevalence of Notch1 and Notch4 basal activation in a large panel of cancer cells lines, suggesting its role in cellular activities of cancer cells. Since Notch inhibition is currently an interesting topic for antitumor therapy, this study could help to discriminate the tumor types or tumor characteristics that are good candidate for Notch inhibition in the clinics. Citation Format: Lucile Astorgues-Xerri, Mathieu Martinet, Jinan Abdullah, Sandrine Faivre, Eric Raymond, Annemilaï Tijeras-Raballand. Involvement of Notch signaling pathway in a panel of human cancer cell lines [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 2501.