Endostatin inhibits adhesion of endothelial cells to collagen I via α2β1 integrin, a possible cause of prevention of chondrosarcoma growth

Takayuki Furumatsu, Noriko Yamaguchi, Keiichiro Nishida, Akira Kawai, Toshiyuki Kunisada, Masayoshi Namba, Hajime Inoue, Yoshifumi Ninomiya

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Endostatin derived from collagen XVIII is a potent endogenous anti-angiogenic factor that induces regression of various tumors of epithelial origin. Endostatin has been shown to inhibit endothelial cell functions, however, its effect remains controversial. We first attempted here to apply the inhibitory effect of recombinant human endostatin on chondrosarcomas, which originate from the mesenchyme, in nude mice. Endostatin induced reduction of chondrosarcoma growth and tumor angiogenesis in vivo. However, endostatin showed no effect on the proliferation and migration of chondrosarcoma cells in vitro. Next, we investigated the interactions between endostatin and endothelial cells in detail. Endostatin inhibited the migration on and attachment to collagen I but did not affect the proliferation of endothelial cells. Although the migration of endothelial cells was stimulated by angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor, endostatin showed similar inhibitory effects on it in the presence and absence of the stimulants. Moreover, the inhibitory effect against endothelial cell attachment to collagen I was attenuated or modulated in the presence of neutralizing antibodies of α2, α5β1, and αVβ3 integrins but not that of α1 integrin. Our results suggest that endostatin might suppress the α2β1 integrin function of endothelial cells via α5β1 or αVβ3 integrin. We propose here that endostatin might be effective for anti-angiogenic therapy for human chondrosarcomas through the suppression of α2β1 integrin functions in endothelial cells.

Original languageEnglish
Pages (from-to)619-626
Number of pages8
JournalJournal of biochemistry
Volume131
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • Basic fibroblast growth factor
  • Chondrosarcoma
  • Endostatin
  • Integrin
  • Tumor angiogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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