Abstract 2934: The role of Globo H in cancer cell survival

Abstract

Abstract BACKGROUND: Globo H (GH), a glycosphingolipid (GSL) carbohydrate antigen, is found on a variety of epithelial tumors and is a promising target for cancer immunotherapy given the marked difference in expression of GH between cancer cells and normal tissues. Globo series antigens (Globo H, SSEA-4) have been implicated in playing important roles in protecting tumor cells from apoptosis, suppression of immune cell activity in the tumor microenvironment, and promoting endothelial cell angiogenesis through shedding the glycosphingolipids to immune cells and endothelial cells, respectively. Recently, apoptosis regulation by protein interaction with Globo-series GSLs in breast cancer cells was reported. This study aims to investigate the GH and anti-GH antibody effects on cancer cell survival. METHODS: In vivo: After allografting murine B16F10 melanoma subcutaneously, C57BL/6 mice, n=5, were treated with Globo-H ceramide (GHCer) by peritumoral injection and monitored for 26 days. In vitro: GH expression on the surface of tumor cells and colony formative activity in GHCer-treated human cells were measured. Cytokine antibody array and Microwestern protein array analyses were performed in the GHCer-treated A549 cells. Cell viability in high GH–expressing lung cancer cells treated with erlotinib was assessed. Erlotinib resistance and cytokine levels in high GH–expressing tumor cells treated with anti-GH antibody were measured. RESULTS: In vivo: GHCer-treated mice showed accelerated B16F10-tumor growth rates (3.36-fold; P<0.01, n=5) with less tumor necrosis and higher proliferating cell nuclear antigen expression in the internal tumor tissues. In vitro: In GHCer-treated human lung cancer A549 and breast cancer MDA-MB-231 cells, higher colony formative activity and increased exogenous GH expression on the surface of tumor cells compared to the control group were observed, while cell proliferation was not enhanced. Up-regulated erlotinib-resistant cytokine IL-8 and FGF2 and K-RAS-related signaling were observed in A549 cells with exogenous high GH expression. Exogenously GHCer-added lung cancer cells displayed higher cell viability (37.8% increase) during erlotinib challenge, and an anti-GH antibody treatment decreased the GH effects of erlotinib resistance. CONCLUSION: GH promotes cancer cell viability in vitro and in vivo, indicating an important role in cancer cell survival during tumor progression. Anti-GH antibody treatment was shown to be able to abolish the GH effects on erlotinib resistance of lung cancer cells in vitro. Citation Format: Tzer-Min Kuo, Yi-Chien Tsai, Chin-Chan Lee, Jiann-Shiun Lai. The role of Globo H in cancer cell survival [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2934.