The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor

Noona Ambartsumian, Jörg Klingelhöfer, Mariam Grigorian, Claus Christensen, Marina Kriajevska, Eugene Tulchinsky, Georgii Georgiev, Vladimir Berezin, Elisabeth Bock, Jørgen Rygaard, Renhai Cao, Yihai Cao, Eugene Lukanidin

Research output: Contribution to journalArticlepeer-review

204 Citations (Scopus)

Abstract

The involvement of Mts1(S100A4), a small Ca2+-binding protein in tumor progression and metastasis had been demonstrated. However, the mechanism by which mts1(S100A4) promoted metastasis had not been identified. Here we demonstrated that Mts1(S100A4) had significant stimulatory effect on the angiogenesis. We detected high incidence of hemangiomas - benign tumors of vascular origin in aged transgenic mice ubiquitously expressing the mts1(S100A4) gene. Furthermore, the serum level of the Mts1(S100A4) protein increased with ageing. Tumors developed in Mts1-transgenic mice revealed an enhanced vascular density. We showed that an oligomeric, but not a dimeric form of the Mts1(S100A4) protein was capable of enhancing the endothelial cell motility in vitro and stimulate the corneal neovascularization in vivo. An oligomeric fraction of the protein was detected in the conditioned media as well as in human serum. The data obtained allowed us to conclude that mts1(S100A4) might induce tumor progression via stimulation of angiogenesis.

Original languageEnglish
Pages (from-to)4685-4695
Number of pages11
JournalOncogene
Volume20
Issue number34
DOIs
Publication statusPublished - Aug 2 2001
Externally publishedYes

Keywords

  • Angiogenesis
  • S100A4
  • Stimulation of motility

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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