Enhanced Cancer Metastasis in Mice Deficient in Vasohibin-1 Gene

Soichi Ito, Hiroki Miyashita, Yasuhiro Suzuki, Miho Kobayashi, Susumu Satomi, Yasufumi Sato

研究成果: Article査読

17 被引用数 (Scopus)

抄録

Vasohibin-1 (VASH1) is isolated as an endogenous angiogenesis inhibitor produced by the vascular endothelium. We previously reported that tumor growth and tumor angiogenesis were augmented in VASH1 (-/-) mice. Here we examined whether VASH1 plays any role in cancer metastasis. When Lewis lung carcinoma (LLC) cells were inoculated in the footpad to observe spontaneous metastasis, a significant increase in lung metastasis together with inguinal lymph node metastasis was evident in the VASH1 (-/-) mice. Histological analyses revealed that vessels of the footpad tumor in VASH1 (-/-) mice were more immature, having fewer mural cells. However, when LLC cells were injected into a tail vein, the extent of lung metastasis was unchanged between wild-type mice and VASH1 (-/-) mice. When VASH1 in endothelial cells in culture was knocked-down by siRNA, we observed a decrease in the content of ZO-1, a component of tight junctions, which decrease resulted in increased transmigration of cancer cells across the endothelial cell monolayer. These results indicate that endogenous VASH1 tightens the endothelial barrier and makes tumor vessels resistant to cancer metastasis.

本文言語English
論文番号e73931
ジャーナルPloS one
8
9
DOI
出版ステータスPublished - 2013 9 16

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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