The Foxc2 transcription factor regulates tumor angiogenesis

Hideto Sano, Jared P. LeBoeuf, Sergey V. Novitskiy, Seungwoon Seo, Snjezana Zaja-Milatovic, Mikhail M. Dikov, Tsutomu Kume*

*Corresponding author for this work

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)201-206
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume392
Issue number2
DOIs
StatePublished - Feb 5 2010

Keywords

  • Dll4
  • Endothelial cell
  • Forkhead
  • PDGF
  • Tumor angiogenesis
  • VEGF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Sano, H., LeBoeuf, J. P., Novitskiy, S. V., Seo, S., Zaja-Milatovic, S., Dikov, M. M., & Kume, T. (2010). The Foxc2 transcription factor regulates tumor angiogenesis. Biochemical and Biophysical Research Communications, 392(2), 201-206. https://doi.org/10.1016/j.bbrc.2010.01.015