Angiogenesis in a human neuroblastoma xenograft model: Mechanisms and inhibition by tumour-derived interferon-γ

D. Ribatti, B. Nico, A. Pezzolo, A. Vacca, R. Meazza, R. Cinti, B. Carlini, F. Parodi, V. Pistoia, M. V. Corrias

Research output: Contribution to journalArticlepeer-review

Abstract

Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-γ (IFN-γ) gene transfer dampens ACN tumorigenicity. As IFN-γ represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-γ and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-γ xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-γ xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-γ was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds.

Original languageEnglish
Pages (from-to)1845-1852
Number of pages8
JournalBritish Journal of Cancer
Volume94
Issue number12
DOIs
Publication statusPublished - Jun 19 2006

Keywords

  • Angiostatic
  • Endothelial cells
  • Interferon-γ
  • Neuroblastoma
  • Tumour

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Angiogenesis in a human neuroblastoma xenograft model: Mechanisms and inhibition by tumour-derived interferon-γ'. Together they form a unique fingerprint.

Cite this