Abstract 472: Galectin-3 modulates glioblastomas (GBM) tumor microenvironment, and is linked to glioblastoma invasion

Abstract

Abstract Malignant glioblastomas (GBM) are lethal form of brain tumors, and are difficult to treat due to their invasion into the brain parenchyma. Aggressive and invasive nature of GBM is at least partly attributable to GBM associated stem cells (GSC). Soluble factors released by GBM and GSC can recruit inflammatory cells, including brain resident microglia to tumor micro-environment (TME) that support angiogenesis and invasion. We have previously shown that exogenous Galectin-3 (Gal-3), a carbohydrate binding lectin increases the migratory potential of BV2 microglial cells, and promotes the formation of pro-angiogenic structures in an in vitro HUVEC culture and 3D matrigel model. Furthermore, Gal-3 supports the survival of microglial cells under hypoxic environment. In this study, we investigated the role of Gal-3 in GBM by utilizing the biochemical and molecular approaches. Using well characterized GBM tumor cell lines, and GSC lines that exhibit various degrees of invasive potential, we have identified that the expression of the Gal-3 is significantly up-regulated in GSCs that are highly invasive as compared to those that form only focal tumors in a mouse xenotransplantation model. Gal-3 is also highly expressed in microglia that accumulated in and around the GSC tumors in mouse brain, as indicated by co-localization of Gal-3 and Iba1, the maker for activated microglia. Furthermore, Gal-3 expression is significantly increased in GBM tumor cells when exposed to in vitro hypoxic conditions. Importantly, Gal-3 increased the migratory potential of GBM tumor cells in vitro, indicating its role as a chemo-attractant. Taken together, these results suggest that Gal-3 plays a critical role in promoting GBM invasion through modulating the interaction of microglia in TME and GBM. Thus Gal-3 may be a potential therapeutic target for GBM. Citation Format: Umadevi V. Wesley, Esat Resad, Paul Clark, Carolina Larrain, John Kuo, Robert J. Dempsey. Galectin-3 modulates glioblastomas (GBM) tumor microenvironment, and is linked to glioblastoma invasion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 472. doi:10.1158/1538-7445.AM2015-472