Multinucleated Cells Resistant to Genotoxic Factors within Human Glioblastoma Cell Lines

Abstract

Glioblastoma tumors are characterized by a high phenotype diversity among patients and by a high cellular heterogeneity within each tumor instance. Here, we report the effects of photon irradiation of various dosage and regime onto cells of two reference (T98G and A172) and two novel (T2 and R1) human glioblastoma cell lines. In contrast to the A172 and R1 lines, where all cells were perished upon relatively low-dose irradiation, a population of resistant cells within the T98G and T2 lines survived even after a high-dose irradiation. These radio-resistant cells were large single- or multinucleated non-proliferating cells, that remained viable over one month after irradiation. The cells had markedly elevated expression levels of genes coding for factors promoting growth and angiogenesis, components of the extracellular matrix, and marker genes in-herent for mesenchymal phenotype. The expression profile of these genes in the radiation-induced growth-arrested cells T98G and Т2 was similar to that of the cell lines treated with another genotoxic factor, the fotemustine. Therefore, radio-resistant growth-arrested cells are characterized by a high activity of genes encoding proteins affecting both the tumor cells and their microenvironment.