TRAIL inhibits angiogenesis stimulated by VEGF expression in human glioblastoma cells

G. Cantarella, N. Risuglia, R. Dell'Eva, L. Lempereur, A. Albini, G. Pennisi, G. M. Scoto, D. N. Noonan, R. Bernardini

Research output: Contribution to journalArticle

Abstract

Tumour growth is tightly related to new blood vessel formation, tissue remodelling and invasiveness capacity. A number of tissular factors fuel the growth of glioblastoma multiforme, the most aggressive brain neoplasm. In fact, gene array analyses demonstrated that the proapoptotic cytokine tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) inhibited mRNA expression of VEGF, along with those of matrix metalloproteinase-2 (MMP-2), its inhibitor tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), as well as the tumour invasiveness-related gene secreted protein acid rich in cysteine (SPARC) in different human glioblastoma cell lines. Particularly, VEGF mRNA and protein expression and release from glioblastoma cells were also inhibited by TRAIL. The latter also exerted antimitogenic effects on human umbilical vein endothelial cells (HUVECs). With the same cells, TRAIL inhibited new vessel formation in the in vitro matrigel model, as well as it exerted powerful inhibition of blood vessel formation induced by an angiogenic cocktail administered in subcutaneous pellets in vivo in the C57 mouse. Moreover, the expression of MMP-2, its inhibitor TIMP-2 and the tumour invasiveness-related protein SPARC were effectively inhibited by TRAIL in glioblastoma cell lines. In conclusion, our data indicate that TRAIL inhibits the orchestra of factors contributing to glioblastoma biological aggressiveness. Thus, the TRAIL system could be regarded as a molecular target to exploit for innovative therapy of this type of tumour.

Original languageEnglish
Pages (from-to)1428-1435
Number of pages8
JournalBritish Journal of Cancer
Volume94
Issue number10
DOIs
Publication statusPublished - May 22 2006

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Keywords

  • Brain tumour
  • Endothelial cell
  • Invasiveness
  • Tissue remodelling

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cantarella, G., Risuglia, N., Dell'Eva, R., Lempereur, L., Albini, A., Pennisi, G., Scoto, G. M., Noonan, D. N., & Bernardini, R. (2006). TRAIL inhibits angiogenesis stimulated by VEGF expression in human glioblastoma cells. British Journal of Cancer, 94(10), 1428-1435. https://doi.org/10.1038/sj.bjc.6603092