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

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Abstract

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.

Original languageEnglish
Pages (from-to)6651-6657
Number of pages7
JournalCancer Research
Volume63
Issue number20
Publication statusPublished - 2003 Oct 15

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ito, Y., Oike, Y., Yasunaga, K., Hamada, K., Miyata, K., Matsumoto, S. I., Sugano, S., Tanihara, H., Masuho, Y., & Suda, T. (2003). Inhibition of Angiogenesis and Vascular Leakiness by Angiopoietin-Related Protein 4. Cancer Research, 63(20), 6651-6657.