Abstract 1303: Targeted inhibition of galectin-1 suppresses glioblastoma growth

Abstract

Abstract Background: Galectin-1 (Gal1), a carbohydrate-binding protein is implicated in cancer cell proliferation, invasion and tumor angiogenesis. An earlier report from our laboratory demonstrated that glioblastoma (GB) cells express high levels of Gal-1, which promotes tumor progression through upregulation of CXCR4 viaNF-κB in in vitro GB models. Recently, several Gal1-targeting compounds have emerged. OTX008 is a calixarene derivative designed to bind the Gal1 amphipathic β-sheet conformation. Our study aimed to validate the effect of the non-peptidic galectin-1 inhibitor OTX008 in human GB in relevant pre-clinical models. Methods: In vitro cell culture and in vivo GL261 murine models of GB were utilized to assess efficacy of treatment with OTX008 via Alzet osmotic pumps. To investigate the mechanistic effect of OTX008 on GB cells, we used RT-PCR and western blots techniques. Magnetic resonance imaging (MRI), and immunohistochemistry (IHC)-staining methods were used to detect tumor growth in in vivo GL261 murine model following OTX008 treatments. Results: In cultured human and mouse GB cells, OTX008 inhibited proliferation and invasion at micromolar concentrations. We also found that the anti-proliferative effects correlated with Gal1 expression in human and mouse GB cell lines. Furthermore, OTX008 inhibited Gal1 expression and AKT-dependent survival pathways, and decreased CXCR4 expression. In vivo, continued 100ng/kg OTX008 treatment via Alzet osmotic pumps over 14 days reduced tumor growth of GL261 murine model after 3 weeks of implantation. OTX008 treatment was associated with downregulation of Gal1 and Ki67 in treated tumors, as well as decreased micro-vessel density and VEGFR2 expression. Conclusion: These findings suggest that targeting galectin-1 may be an effective approach in the treatment of GB patients. Citation Format: David Cachia, Arindam Rano Chatterjee, William Alex Vandergrift, Sunil J. Patel, Gabriel A. Rabinovich, Arabinda Das. Targeted inhibition of galectin-1 suppresses glioblastoma growth [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 1303.