CD44-associated radioresistance of glioblastoma in irradiated brain areas with optimal tumor coverage

Glioblastoma multiforme (GBM) requires radiotherapy (RT) as its definitive management. However, GBM still has a high local recurrence rate even after RT. Cancer stem-like cells (CSCs) might enable GBM to evade irradiation damage and cause therapeutic failure. The optimal RT plan should achieve a planning target volume (PTV) coverage of more than 95% but cannot always meet the requirements. Here, we demonstrate that irradiation with different tumor coverage rates to different brain areas has similar effects on GBM. To retrospectively analyze the relationship between PTV coverage and the survival rate in 26 malignant glioblastoma patients, we established primary cell lines from patient-derived malignant glioblastoma cells with the PTV₉₅ (PTV coverage of more than 95%) program (GBM-MG1 cells) and the Non-PTV₉₅ (poor PTV coverage of less than 95%) program (GBM-MG2 cells). The clinical results of PTV₉₅ and Non-PTV₉₅ showed no difference in the overall survival (OS) rate (P =.390) between the two different levels of PTV coverage. GBM-MG1 (PTV₉₅ program) cells exhibited higher radioresistance than GBM-MG2 (Non-PTV₉₅ program) cells. CD44 promotes radioresistance, CSC properties, angiogenesis and cell proliferation in GBM-MG1 (PTV₉₅ program) cells. GBM patients receiving RT with the PTV₉₅ program exhibited higher radioresistance, CSC properties, angiogenesis and cell proliferation than GBM patients receiving RT with the Non-PTV₉₅ program. Moreover, CD44 plays a crucial role in these properties of GBM patients with the PTV₉₅ program.