Anti-angiogenic effects of differentiation-inducing factor-1 involving VEGFR-2 expression inhibition independent of the Wnt/β-catenin signaling pathway.

Tatsuya Yoshihara, Fumi Takahashi-Yanaga, Fumie Shiraishi, Sachio Morimoto, Yutaka Watanabe, Masato Hirata, Sumio Hoka, Toshiyuki Sasaguri

研究成果: Contribution to journalArticle査読

17 被引用数 (Scopus)

抄録

Differentiation-inducing factor-1 (DIF-1) is a putative morphogen that induces cell differentiation in Dictyostelium discoideum. DIF-1 inhibits proliferation of various mammalian tumor cells by suppressing the canonical Wnt/β-catenin signaling pathway. To assess the potential of a novel cancer chemotherapy based on the pharmacological effect of DIF-1, we investigated whether DIF-1 exhibits anti-angiogenic effects in vitro and in vivo. DIF-1 not only inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) by restricting cell cycle in the G0/G1 phase and degrading cyclin D1, but also inhibited the ability of HUVECs to form capillaries and migrate. Moreover, DIF-1 suppressed VEGF- and cancer cell-induced neovascularization in Matrigel plugs injected subcutaneously to murine flank. Subsequently, we attempted to identify the mechanism behind the anti-angiogenic effects of DIF-1. We showed that DIF-1 strongly decreased vascular endothelial growth factor receptor-2 (VEGFR-2) expression in HUVECs by inhibiting the promoter activity of human VEGFR-2 gene, though it was not caused by inhibition of the Wnt/β-catenin signaling pathway. These results suggested that DIF-1 inhibits angiogenesis both in vitro and in vivo, and reduction of VEGFR-2 expression is involved in the mechanism. A novel anti-cancer drug that inhibits neovascularization and tumor growth may be developed by successful elucidation of the target molecules for DIF-1 in the future.

本文言語英語
ページ(範囲)245
ページ数1
ジャーナルMolecular cancer
9
DOI
出版ステータス出版済み - 2010

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 腫瘍学
  • 癌研究

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