The first two authors contributed equally to this work.
Cancer Cell Biology
Inhibition of telomerase in the endothelial cells disrupts tumor angiogenesis in glioblastoma xenografts
Article first published online: 20 NOV 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 6, pages 1236–1242, 15 March 2008
How to Cite
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. and Pallini, R. (2008), Inhibition of telomerase in the endothelial cells disrupts tumor angiogenesis in glioblastoma xenografts. Int. J. Cancer, 122: 1236–1242. doi: 10.1002/ijc.23193
- Issue published online: 21 JAN 2008
- Article first published online: 20 NOV 2007
- Manuscript Accepted: 7 AUG 2007
- Manuscript Received: 21 JUN 2007
- FIRB. Grant Number: RBNE01MBEC_003
- Compagnia di San Paolo
- Fondi d'Ateneo linea D1
- ATENA Onlus
- Filas and Fondazione Nando Peretti
- glioblastoma multiforme;
- tumor xenograft
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. © 2007 Wiley-Liss, Inc.