Impaired angiogenesis, delayed wound healing and retarded tumor growth in Perlecan heparan sulfate-deficient mice

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Zhongjun Zhou
  • Jianming Wang
  • Renhai Cao
  • Hiroyuki Morita
  • Raija Soininen
  • Baohua Liu
  • Yihai Cao
  • Karl Tryggvason

Detail(s)

Original languageEnglish
Pages (from-to)4699-4702
Journal / PublicationCancer Research
Volume64
Issue number14
Publication statusPublished - 15 Jul 2004
Externally publishedYes

Abstract

Perlecan, a modular proteoglycan carrying primary heparan sulfate (HS) side chains, is a major component of blood vessel basement membranes. It sequesters growth factors such as fibroblast growth factor 2 (FGF-2) and regulates the ligand-receptor interactions on the cell surface, and thus it has been implicated in the control of angiogenesis. Both stimulatory and inhibitory effects of perlecan on FGF-2 signaling have been reported. To understand the in vivo function of HS carried by perlecan, the perlecan gene heparan sulfate proteoglycan 2 (Hspg2) was mutated in mouse by gene targeting. The HS at the NH2 terminus of perlecan was removed while the core protein remained intact. Perlecan HS-deficient (Hspg2Δ3/Δ3) mice survived embryonic development and were apparently healthy as adults. However, mutant mice exhibited significantly delayed wound healing, retarded FGF-2-induced tumor growth, and defective angiogenesis. In the mouse corneal angiogenesis model, FGF-2-induced neovascularization was significantly impaired in Hspg2 Δ3/Δ3 mutant mice. Our results suggest that HS in perlecan positively regulates the angiogenesis in vivo.

Citation Format(s)

Impaired angiogenesis, delayed wound healing and retarded tumor growth in Perlecan heparan sulfate-deficient mice. / Zhou, Zhongjun; Wang, Jianming; Cao, Renhai; Morita, Hiroyuki; Soininen, Raija; Chan, Kui Ming; Liu, Baohua; Cao, Yihai; Tryggvason, Karl.

In: Cancer Research, Vol. 64, No. 14, 15.07.2004, p. 4699-4702.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal