Abstract 9P
Background
Glioblastoma (GBM) is an aggressive and fatal brain cancer in adults with ineffective existing treatment methods. Intracellular adhesion molecule 1 (ICAM1) is a cell adhesion molecule expressed by tumor associated macrophages (TAMs) in GBM. TAMs enhance tumor growth and proliferation, particularly within the characteristic hypoxic tumor microenvironment (TME) of GBM. Hypothesis: 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 tumor cells and macrophages, thereby facilitating the migration, proliferation and invasion of the tumor cells.
Methods
Assess the expression levels of ICAM1 in primary and immortalized human and mouse macrophages under hypoxic conditions (1% O2, 0.2% O2, and HIF stabilizing drug IOX4). Analyze the effect of ICAM1 deficiency, knockdown, and overexpression and hypoxic conditions on macrophage behaviour including migration, proliferation, and adhesion to tumor cells. Intracranially inject ICAM1 deficient mouse model with GBM followed by analysis of tumor growth, overall survival and the composition of the tumor microenvironment.
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 tumor cell-conditioned medium in vitro and is further exacerbated upon incubation of these cells in a hypoxic chamber at 1% and 0.2% oxygen levels and treatment of HIF-stabilizing drug IOX4. The migration levels and proliferation rate of macrophages is higher in wild type cells than in ICAM1 deficient cells. Macrophage migration and proliferation levels increase when co-cultured with tumor cell condition media and is further exacerbated upon incubation of these cells in hypoxic conditions. ICAM1 deficient mice succumbed to GBM more quickly than wild type mice.
Conclusions
It is evident that the hypoxic tumor microenvironment increases the expression of ICAM1 in macrophages. The expression of ICAM1 in TAMs in hypoxic TME promotes GBM cell invasiveness and migration.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Gelareh Zadeh.
Funding
CIHR.
Disclosure
The author has declared no conflicts of interest.