Inhibition of Angiogenesis and Vascular Leakiness by Angiopoietin-Related Protein 4

Yasuhiro Ito, Yuichi Oike, Kunio Yasunaga, Koichi Hamada, Keishi Miyata, Shun Ichiro Matsumoto, Sumio Sugano, Hidenobu Tanihara, Yasuhiko Masuho, Toshio Suda

研究成果: Article査読

162 被引用数 (Scopus)


Angiopoietins and angiopoietin-related proteins (ARPs) have been shown to regulate angiogenesis, a process essential for various neovascular diseases including tumors. Here, we identify ARP4/fasting-induced adipose factor/peroxisome proliferator-activated receptor γ angiopoietin-related as a novel antiangiogenic modulatory factor. We hypothesized that ARP4 may regulate angiogenesis. In vitro experiments using purified recombinant ARP4 protein revealed that ARP4 markedly inhibited the proliferation, chemotaxis, and tubule formation of endothelial cells. Moreover, using corneal neovascularization and Miles permeability assays, we found that both vascular endothelial growth factor-induced in vivo angiogenesis and vascular leakiness were significantly inhibited by the addition of ARP4. Finally, we found remarkable suppression of tumor growth within the dermal layer associated with decreased numbers of invading blood vessels in transgenic mice that express ARP4 in the skin driven by the keratinocyte promoter. These findings demonstrate that ARP4 functions as a novel antiangiogenic modulatory factor and indicate a potential therapeutic effect of ARP4 in neoplastic diseases.

ジャーナルCancer Research
出版ステータスPublished - 2003 10月 15

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究


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