Inhibition of telomerase in the endothelial cells disrupts tumor angiogenesis in glioblastoma xenografts

Maria Laura Falchetti, Maria Patrizia Mongiardi, Paolo Fiorenzo, Giovanna Petrucci, Francesco Pierconti, Igea D'Agnano, Giorgio D'Alessandris, Giulio Alessandri, Maurizio Gelati, Lucia Ricci-Vitiani, Giulio Maira, Luigi Maria Larocca, Andrea Levi, Roberto Pallini

Research output: Contribution to journalArticle

Abstract

Tumor angiogenesis is a complex process that involves a series of interactions between tumor cells and endothelial cells (ECs). In vitro, glioblastoma multiforme (GBM) cells are known to induce an increase in proliferation, migration and tube formation by the ECs. We have previously shown that in human GBM specimens the proliferating ECs of the tumor vasculature express the catalytic component of telomerase, hTERT, and that telomerase can be upregulated in human ECs by exposing these cells to GBM in vitro. Here, we developed a controlled in vivo assay of tumor angiogenesis in which primary human umbilical vascular endothelial cells (HUVECs) were subcutaneously grafted with or without human GBM cells in immunocompromised mice as Matrigel implants. We found that primary HUVECs did not survive in Matrigel implants, and that telomerase upregulation had little effect on HUVEC survival. In the presence of GBM cells, however, the grafted HUVECs not only survived in Matrigel implants but developed tubule structures that integrated with murine microvessels. Telomerase upregulation in HUVECs enhanced such effect. More importantly, inhibition of telomerase in HUVECs completely abolished tubule formation and greatly reduced survival of these cells in the tumor xenografts. Our data demonstrate that telomerase upregulation by the ECs is a key requisite for GBM tumor angiogenesis.

Original languageEnglish
Pages (from-to)1236-1242
Number of pages7
JournalInternational Journal of Cancer
Volume122
Issue number6
DOIs
Publication statusPublished - Mar 15 2008

Keywords

  • Glioblastoma multiforme
  • HUVEC
  • Telomerase
  • Tumor xenograft

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Falchetti, M. L., Mongiardi, M. P., Fiorenzo, P., Petrucci, G., Pierconti, F., D'Agnano, I., D'Alessandris, G., Alessandri, G., Gelati, M., Ricci-Vitiani, L., Maira, G., Larocca, L. M., Levi, A., & Pallini, R. (2008). Inhibition of telomerase in the endothelial cells disrupts tumor angiogenesis in glioblastoma xenografts. International Journal of Cancer, 122(6), 1236-1242. https://doi.org/10.1002/ijc.23193