Microenvironmental regulation of tumor infiltration in radioresistant glioma cells

Glioblastoma, is the most frequent and malignant primary brain tumor. Despite modern surgical and medical treatments, GBM still remains an incurable brain disease. Post-operative radiotherapy extends survival, but median survival is still less than 15 months, and long-term survival is extremely rare. The accumulated evidence suggests that although ionizing radiation which is one of therapies of GBM is widely used for the treatment of glioblastoma (GBM), the effect of radiation on patient survival is marginal and upon recurrence tumors frequently shift towards mesenchymal subtype adopting invasiveness. As the most cause of this, it was presented that radiation therapeutic research focused entirely on the cancer cells itself in augmenting radiotherapy effects, ignoring the complex biological crosstalk between the tumor cells and its surrounding stroma. In this doctoral work, it was attempted to approach the relationship between radio resistant GBM cells and immune cells or ECM components in tumor microenvironment. In other words, It was suggested how stroma in tumor microenvironment is altered by resistant GBM cells and regulate GBM cells. Importantly, It was demonstrated that (1) oncogenic route between sICAM-1 and wnt3a in cellular communication or (2) increased the production of extracellular matrix component hyaluronic acid (HA) in the tumor microenvironment is important in the acquisition of invasiveness of GBM cells after radiation. Collectively, this study suggest that a combination of radiotherapy and targeting sICAM-1 and Hyaluronic acid (HA) may improve therapeutic interventions, dampening the harmful-effects of radiotherapy in glioma treatment.Docto