Targeting telomeres in brain vasculature does not impede initiation and progression of glioblastoma.

Abstract

The tumor microenvironment is proposed to have an essential role in the growth and therapeutic response of glioblastoma. Vessel formation or angiogenesis has been an important target of different therapeutic strategies. In the past, we described that targeting telomere protection through abrogation or inhibition of the TRF1 shelterin telomere protein in a GBM model is sufficient to delay tumor growth and progression. Here, we set out to address whether Trf1 deletion only in endothelial cells has an impact on GBM growth and progression. Although we saw a tendency to a decrease in CD31-positive cells in GBM tumors where Trf1 was deleted, which was concomitant with a tendency to increased global DNA damage and increased telomere induced DNA damage foci in endothelial cells, as expected from telomere unprotection, this was not sufficient to delay tumor growth and progression. These findings suggest that TRF1-dependent telomere protection in endothelial cells is not a major limiting factor for PDGF-driven GBM at tumor initiation and progression.