CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma

Rosalinda Sorrentino, Silvana Morello, Maria Grazia Giordano, Claudio Arra, Piera Maiolino, Ian M. Adcock, Aldo Pinto

Research output: Contribution to journalArticle

Abstract

Vascular endothelial-derived growth factor (VEGF) plays a fundamental role in the formation of new vessels within the tumour mass. Increasing evidence has highlighted the involvement of Toll-like receptors (TLRs) in cancer. Of interest, TLR9 is over-expressed in human lung carcinoma tissues. The aim of our study was to determine whether TLR9 activation could alter VEGF release in a mouse model of lung carcinoma. Lewis lung carcinoma cells were intravenously (i.v.) inoculated and 10 days later, tumour-bearing mice were treated with CpG-ODN (CpG, a TLR9 ligand) or PBS. CpG administration enhanced VEGF release, which was associated with increased tumour lesions in the lung. CpG induced high levels of IL-6 expression and activation of STAT3 in tumour-bearing mice. Moreover, CpG induced VEGF release from primary fibroblasts and endothelial cells, which correlated with IL-6 and TGFβ production. This may explain the large influx of fibroblasts and the production of basic fibroblast growth factor (bFGF) in the tumour mass. The administration of a monoclonal antibody against VEGF A arrested tumour progression and induced a Th1-like response in CpG-treated tumour-bearing mice. In conclusion, our study demonstrates that the combination of CpG with anti-VEGF monoclonal antibody could be of potential therapeutic in lung carcinoma.

Original languageEnglish
Pages (from-to)2815-2822
Number of pages8
JournalInternational Journal of Cancer
Volume128
Issue number12
DOIs
Publication statusPublished - Jun 15 2011

Keywords

  • angiogenesis
  • CpG
  • lung carcinoma
  • toll-like receptors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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