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VEGF receptor signaling links inflammation and tumorigenesis in colitis-associated cancer.

Authors: Waldner, MJ  Wirtz, S  Jefremow, A  Warntjen, M  Neufert, C  Atreya, R  Becker, C  Weigmann, B  Vieth, M  Rose-John, S  Neurath, MF 
Citation: Waldner MJ, etal., J Exp Med. 2010 Dec 20;207(13):2855-68. Epub 2010 Nov 22.
Pubmed: (View Article at PubMed) PMID:21098094
DOI: Full-text: DOI:10.1084/jem.20100438

Whereas the inhibition of vascular endothelial growth factor (VEGF) has shown promising results in sporadic colon cancer, the role of VEGF signaling in colitis-associated cancer (CAC) has not been addressed. We found that, unlike sporadic colorectal cancer and control patients, patients with CAC show activated VEGFR2 on intestinal epithelial cells (IECs). We then explored the function of VEGFR2 in a murine model of colitis-associated colon cancer characterized by increased VEGFR2 expression. Epithelial cells in tumor tissue expressed VEGFR2 and responded to VEGF stimulation with augmented VEGFR2-mediated proliferation. Blockade of VEGF function via soluble decoy receptors suppressed tumor development, inhibited tumor angiogenesis, and blocked tumor cell proliferation. Functional studies revealed that chronic inflammation leads to an up-regulation of VEGFR2 on IECs. Studies in conditional STAT3 mutant mice showed that VEGFR signaling requires STAT3 to promote epithelial cell proliferation and tumor growth in vivo. Thus, VEGFR-signaling acts as a direct growth factor for tumor cells in CAC, providing a molecular link between inflammation and the development of colon cancer.

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CRRD Object Information
CRRD ID: 5684533
Created: 2011-12-21
Species: All species
Last Modified: 2011-12-21
Status: ACTIVE



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