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

12 Citations (Scopus)

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

Fingerprint

Vascular Endothelial Growth Factor A
Carcinoma
Lung
Neoplasms
Interleukin-6
Fibroblasts
Monoclonal Antibodies
Lewis Lung Carcinoma
Toll-Like Receptors
Fibroblast Growth Factor 2
Endothelial Cells
Ligands

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma. / Sorrentino, Rosalinda; Morello, Silvana; Giordano, Maria Grazia; Arra, Claudio; Maiolino, Piera; Adcock, Ian M.; Pinto, Aldo.

In: International Journal of Cancer, Vol. 128, No. 12, 15.06.2011, p. 2815-2822.

Research output: Contribution to journalArticle

Sorrentino, R, Morello, S, Giordano, MG, Arra, C, Maiolino, P, Adcock, IM & Pinto, A 2011, 'CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma', International Journal of Cancer, vol. 128, no. 12, pp. 2815-2822. https://doi.org/10.1002/ijc.25626
Sorrentino, Rosalinda ; Morello, Silvana ; Giordano, Maria Grazia ; Arra, Claudio ; Maiolino, Piera ; Adcock, Ian M. ; Pinto, Aldo. / CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma. In: International Journal of Cancer. 2011 ; Vol. 128, No. 12. pp. 2815-2822.
@article{59eaad46ac65466c9a881c580626e77f,
title = "CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma",
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.",
keywords = "angiogenesis, CpG, lung carcinoma, toll-like receptors",
author = "Rosalinda Sorrentino and Silvana Morello and Giordano, {Maria Grazia} and Claudio Arra and Piera Maiolino and Adcock, {Ian M.} and Aldo Pinto",
year = "2011",
month = "6",
day = "15",
doi = "10.1002/ijc.25626",
language = "English",
volume = "128",
pages = "2815--2822",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "12",

}

TY - JOUR

T1 - CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma

AU - Sorrentino, Rosalinda

AU - Morello, Silvana

AU - Giordano, Maria Grazia

AU - Arra, Claudio

AU - Maiolino, Piera

AU - Adcock, Ian M.

AU - Pinto, Aldo

PY - 2011/6/15

Y1 - 2011/6/15

N2 - 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.

AB - 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.

KW - angiogenesis

KW - CpG

KW - lung carcinoma

KW - toll-like receptors

UR - http://www.scopus.com/inward/record.url?scp=79955408975&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955408975&partnerID=8YFLogxK

U2 - 10.1002/ijc.25626

DO - 10.1002/ijc.25626

M3 - Article

C2 - 20725994

AN - SCOPUS:79955408975

VL - 128

SP - 2815

EP - 2822

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 12

ER -