Cancer- related protein profile of patient-derived and commercial glioblastoma cell lines exposed to Temozolomide

Abstract

Purpose Since recurrence is observed in almost all glioma patients deeper insight into mechanisms responsible for therapy resistance and identification of new biomarkers is urgently required. In this study were analyzed differences in expression of 84 cancer- related proteins in three GBM cell lines: the commercial T98G cells and two patient-derived cell lines. Materials and Methods Influence of temozolomide (TMZ) on changes in proteins expression, cell morphology and migration was investigated. Analyzed lines were characterized by different remarkable plasticity of proteins expression and proteomic alterations induced by TMZ. Among 10 proteins expressed in all lines, 5 (Cathepsin b, FGF, Survivin, AXL, Osteopontin) were modulated by TMZ administration. Results As a result of TMZ exposition in both HROG02 and T98G cell lines proteins involved in chemoresistance and invasion (TIE-2, Thrombospondin) were detected. This suggests that TMZ promoted their malignant phenotype even further. In control culture (not subjected to TMZ) of HROG17 cells proteins involved in metabolism were strongly suppressed. Conclusion The presented data shed a new light on the immunometabolic profile of glioma proteome and its plasticity in response to Temozolomide interventions. Cathepsin b, FGF, Survivin, AXL and Osteopontin seem to be promising targets for a multimodal treatment that could be applied to inhibit GBM recurrence in the future.