BSCI-14 THE ROLE OF ICAM1 IN GLIOBLASTOMA TUMOUR ASSOCIATED MACROPHAGES UNDER HYPOXIC CONDITIONS

Abstract

Abstract BACKGROUND Glioblastoma (GBM) is an aggressive and highly fatal brain cancer in adults. Existing treatment methods are ineffective and we are in need of new treatments that extend the overall survival and improve quality-of-life. Cell adhesion molecules (CAMs) are proteins that enable cells to communicate with one another and the surrounding environment. Intracellular adhesion molecule 1 (ICAM1) is a CAM expressed by TAMs in GBM. Tumour associated macrophages (TAMs) are thought to enhance tumour growth and proliferation, particularly within the characteristic hypoxic tumour microenvironment (TME) of GBM. I hypothesize that the expression of ICAM1 on the surface of TAMs contributes to GBM cell invasiveness, especially in the hypoxic TME, by enhancing the interaction between tumour cells and macrophages, thereby facilitating the migration and invasion of the tumour cells. METHODOLOGY Assess the expression levels of ICAM1 in primary and immortalized human and mouse macrophages under hypoxic conditions. Analyze the effect of ICAM1 deficiency on macrophage behaviour including migration, proliferation, and adhesion to tumour cells. Intracranially inject GL261 glioma cells in ICAM1 deficient and wild type mice. RESULTS ICAM1 is highly expressed in different cell types within the GBM microenvironment, including TAMs. The expression is particularly enhanced when primary or immortalized macrophages are treated with tumour cell-conditioned medium and is further exacerbated upon incubation of these cells in hypoxic conditions. The migration levels of bone marrow derived macrophage mouse cell type is higher in wild type cells than in ICAM1 deficient cells and higher when co-cultured with tumour cell condition media. ICAM1 deficient mice succumbed to GBM more quickly compared with wild type. CONCLUSIONS It is evident that the hypoxic tumour microenvironment increases the expression of ICAM1 in macrophages. The tumour microenvironment increases migration levels of macrophages. The expression of ICAM1 in TAMs in hypoxic TME promotes GBM cell invasiveness, proliferation, aggressiveness and migration.