Diameter of tumor blood vessels is a good parameter to estimate HIF-1-active regions in solid tumors

Biochem Biophys Res Commun. 2008 Sep 5;373(4):533-8. doi: 10.1016/j.bbrc.2008.06.062. Epub 2008 Jun 27.


As the transcriptional activity of hypoxia-inducible factor 1 (HIF-1) is associated with resistance of tumor cells to current antitumor therapies, the spatiotemporal dynamics of HIF-1-active regions has been of great interest as a therapeutic target. In the present study, we established a unique cancer cell line, which changes color HIF-1-dependently, and monitored it during tumor progression. In imaging experiments, HIF-1-active cells appeared over the tumor xenograft, but dramatically decreased in number as blood vessels developed around the tumor. The remaining HIF-1-active cells at the center of the xenograft also disappeared after neovascularization. Thereafter, tumor growth was accelerated and HIF-1-active cells reappeared in different regions. The distance between HIF-1-active cells and the nearest vessels correlated to the diameter of the vessel (r=0.801). These results provide a basic knowledge of how to estimate the spatiotemporal dynamics of HIF-1-active cells using information about the image-guided architecture of tumor blood vessels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor*
  • HeLa Cells
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Luminescent Proteins / analysis
  • Mice
  • Neoplasm Transplantation
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology*
  • Xenograft Model Antitumor Assays


  • Hypoxia-Inducible Factor 1
  • Luminescent Proteins