Examining the role of communication between Glioblastoma (GBM) cellular subpopulations in the induced migration and survival of the tumor in response to irradiation.

Introduction: Tumor heterogeneity plays a crucial role in Glioblastoma (GBM) growth, progression and resistance to therapy. We have recently shown that an aggressive subpopulation expressing constitutively active Epidermal Growth Factor Receptor (EGFRvIII) within GBM tumor increases the infiltrative properties of EGFRwt cells (overexpressing EGFR) through paracrine secretion of IL6 and HGF. We hypothesized that this communication may play an important role in GBM response to irradiation. Though radiation is a part of GBM treatment, radiotherapy (RT) has been found to promote tumor invasion. In this study, we aim to develop a strategy for GBM sensitization to radiotherapy through inhibition of altered migration proteins.

Materials and Methods: In order to examine whether the communication between two different GBM subpopulations may influence the motility of the irradiated cells, EGFRvIII and EGFRwt cells were seeded either alone or in co-culture and their migratory phenotypes were examined. Under irradiation at different doses cells were analyzed using scratch assay.

Results: Following RT we noticed that 5 Gy induces an aggressive phenotype in terms of invasion. My preliminary results show that the velocity and infiltrative properties of EGFRwt cells are induced when they are co-cultured with EGFRvIII cells. Moreover survival of the co-culture increases under RT.

Conclusions: Communication between GBM subpopulations may play an important role in the induced migration and survival of GBM cells in response to irradiation. We aim to find key proteins mediating those phenotypes and through which RT treatment can be optimized.