Title : Neurosteroid ganaxolone attenuates beta-amyloid toxicity by activating the liver X receptor in alzheimer’s disease
Abstract:
Glioblastoma (GBM) is a fatal brain cancer in adults with ineffective existing treatment methods. Cell adhesion molecules (CAMs) are proteins that are expressed on the surface of cells and enable them to communicate and interact with one another and the surrounding environment. Intracellular adhesion molecule 1 (ICAM-1) is a cell adhesion molecule expressed by macrophages, tumor cells and endothelial cells in GBM. Preliminary data showed that ICAM-1 is associated with poorer overall and progression free survival in GBM patients and ICAM-1 expression levels increase in recurrent GBM tumors. TAMs enhance tumor growth and proliferation, within GBM. The goal of the study is to determine if ICAM-1 expression on TAMs contributes to GBM cell invasiveness in the hypoxic TME and enhances the interaction between tumor cells and macrophages, facilitating the migration, proliferation, and invasion of the tumor cells. It was found that upon incubation of human and mouse macrophages in hypoxia, ICAM-1 expression levels increased and were further exasperated upon culturing with tumor cell-conditioned medium. Incubation of wild type and ICAM-1 deficient macrophages in hypoxia resulted in lower migration and proliferation in ICAM-1 deficient cells compared to wild type cells. Cultured with tumor cell condition media, migration and proliferation of ICAM-1 deficient macrophages was lower than wild type macrophages. ICAM-1 deficient mouse model and wild type mice were intracranially injected with mouse glioma cells. It was found that ICAM1 deficient mice survived longer and had lower overall tumor volume than wild type mice. In conclusion, the expression of ICAM1 in TAMs in hypoxic TME promotes GBM cell invasiveness, proliferation, and migration. ICAM-1 plays a role in macrophage migration, proliferation, and its expression on TAMs, resulting in more aggressive tumors. Certain environmental factors like hypoxia enhance the expression of ICAM-1 which is associated with more aggressive features of hypoxic GBM.
Audience Take Away
- The audience will be able to learn more about the mechanism of GBM and the roles of different cell populations (specifically immune cell populations) in its tumorigenesis
- Determine a potentially new therapeutic target for glioblastoma patients to increase overall survival
- Learn the different ways we can approach research to solve novel therapeutic problems
