Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biochem Biophys Res Commun. 2010 Feb 5;392(2):201-6. doi: 10.1016/j.bbrc.2010.01.015. Epub 2010 Jan 12.

The Foxc2 transcription factor regulates tumor angiogenesis.

Author information

  • 1Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, TN 37232-6300, USA.

Abstract

The Forkhead/Fox transcription factor Foxc2 is a critical regulator of vascular development. However, the role of Foxc2 in pathological angiogenesis in cancer remains unknown. Here we show that FoxC2 is highly expressed in human breast and colonic tumors and in the tumor endothelium in human and mouse melanomas. Using the B16 melanoma tumor model, we investigated the function of Foxc2 in tumor angiogenesis. After subcutaneous injection of B16 melanoma cells, primary tumor growth as well as neovascularization was markedly reduced in mice lacking one copy of the Foxc2 gene (Foxc2+/-). Consistently, expression levels of several angiogenic factors, including vascular endothelial growth factor (Vegf), matrix metallopeptidase 2 (Mmp2), and platelet-derived growth factor-B (Pdgfb), were significantly decreased in B16 tumors grown in Foxc2+/- mice, and tumor blood vessels formed in Foxc2+/- mice showed reduced coverage of mural cells and endothelial cell apoptosis. In addition, the tumor tissue in Foxc2+/- mice had an accumulation of necrotic cells. Taken together, these findings demonstrate that haplodeficiency of Foxc2 results in impaired formation of tumor blood vessels as well as reduced tumor growth and thereby provide evidence that Foxc2 is critical for tumor development and angiogenesis.

2010 Elsevier Inc. All rights reserved.

PMID:
20060810
[PubMed - indexed for MEDLINE]
PMCID:
PMC2822046
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk