Involvement of the collagen I-binding motif in the anti-angiogenic activity of pigment epithelium-derived factor

Jun Hosomichi, Norihisa Yasui, Takaki Koide, Kunimichi Soma, Ikuo Morita

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Pigment epithelium-derived factor (PEDF) is the most potent endogenous inhibitor of angiogenesis in age-related macular degeneration and tumors. However, the molecular mechanism of the anti-angiogenic activity of PEDF is poorly understood. PEDF interacts with the extracellular matrix (ECM) in vitro. Here, we investigated the possible involvement of the motif for ECM interaction in the anti-angiogenic activity of PEDF. The growth rates of HeLa cells in culture were not affected by transfection of PEDF, indicating that PEDF did not suppress tumor cell growth directly. In tumor xenografts, the overexpression of wild-type PEDF significantly suppressed tumor growth, whereas a mutant of the collagen I-binding site of PEDF (Col-mut PEDF) did not inhibit tumor growth. A mutant of the heparin-binding site of PEDF (Hep-mut PEDF) suppressed tumor growth. Histological analysis showed that the density and area of microvasculatures in either PEDF or Hep-mut PEDF were suppressed when compared with those in either vector or Col-mut PEDF. Our data indicate that PEDF inhibits tumor growth via its anti-angiogenic activity, and the collagen I-binding motif of PEDF is involved in the biological activity.

Original languageEnglish
Pages (from-to)756-761
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume335
Issue number3
DOIs
Publication statusPublished - Sep 30 2005

Keywords

  • Anti-angiogenesis
  • Collagen I
  • HeLa cell
  • Pigment epithelium-derived factor
  • Tumor growth

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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