Endogenous angiogenesis inhibitor vasohibin1 exhibits broad-spectrum antilymphangiogenic activity and suppresses lymph node metastasis

Takahiro Heishi, Tomoko Hosaka, Yasuhiro Suzuki, Hiroki Miyashita, Yuichi Oike, Takashi Takahashi, Takumi Nakamura, Shingo Arioka, Yuichi Mitsuda, Tomoaki Takakura, Kanji Hojo, Mitsunobu Matsumoto, Chihiro Yamauchi, Hideki Ohta, Hikaru Sonoda, Yasufumi Sato

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57 Citations (Scopus)

Abstract

During cancer progression, the angiogenesis that occurs is involved in tumor growth and hematogenous-distant metastasis, whereas lymphangiogenesis is involved in regional lymph node metastasis. Angiogenesis is counterregulated by various endogenous inhibitors; however, little is known about endogenous inhibitors of lymphangiogenesis. We recently isolated vasohibin1 as an angiogenesis inhibitor intrinsic to the endothelium and further demonstrated its anticancer activity through angiogenesis inhibition. Here, we examined the effect of vasohibin1 on lymphangiogenesis. Vasohibin1 exhibited broad-spectrum antilymphangiogenic activity in the mouse cornea induced by factors including VEGF-A, VEGF-C, FGF2, and PDGF-BB. We then inoculated highly lymph node-metastatic cancer cells into mice and examined the effect of vasohibin1 on lymph node metastasis. Tail-vein injection of adenovirus containing the human vasohibin1 gene inhibited tumor lymphangiogenesis and regional lymph node metastasis. Moreover, local injection of recombinant vasohibin1 inhibited lymph node metastasis. These results suggest vasohibin1 to be the first known intrinsic factor having broad-spectrum antilymphangiogenic activity and indicate that it suppresses lymph node metastasis.

Original languageEnglish
Pages (from-to)1950-1958
Number of pages9
JournalAmerican Journal of Pathology
Volume176
Issue number4
DOIs
Publication statusPublished - 2010 Apr

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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