title: Diameter of tumor blood vessels is a good parameter to estimate HIF-1-active regions in solid tumors.
abstract: 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.
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606 8507, Japan. hharada@kuhp.kyoto-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
authors.forename: Xuejun
authors.initials: X
authors.lastname: Xie
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itasaka
authors.forename: Lihua
authors.initials: L
authors.lastname: Zeng
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Akiyo
authors.initials: A
authors.lastname: Morinibu
authors.forename: Kazumi
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008164:Luminescent Proteins / Q000032:analysis; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D051793:Hypoxia-Inducible Factor 1; D008164:Luminescent Proteins