Anti-angiogenesis and anti-tumor activity of recombinant anginex

Ricardo J.M.G.E. Brandwijk, Ruud P.M. Dings, Edith van der Linden, Kevin H. Mayo, Victor L.J.L. Thijssen, Arjan W. Griffioen

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Anginex, a synthetic 33-mer angiostatic peptide, specifically inhibits vascular endothelial cell proliferation and migration along with induction of apoptosis in endothelial cells. Here we report on the in vivo characterization of recombinant anginex and use of the artificial anginex gene for gene therapy approaches. Tumor growth of human MA148 ovarian carcinoma in athymic mice was inhibited by 80% when treated with recombinant anginex. Histological analysis of the tumors showed an approximate 2.5-fold reduction of microvessel density, suggesting that angiogenesis inhibition is the cause of the anti-tumor effect. Furthermore, there was a significant correlation between the gene expression patterns of 16 angiogenesis-related factors after treatment with both recombinant and synthetic anginex. To validate the applicability of the anginex gene for gene therapy, stable transfectants of murine B16F10 melanoma cells expressing recombinant anginex were made. Supernatants of these cells inhibited endothelial cell proliferation in vitro. Furthermore, after subcutaneous injection of these cells in C57BL/6 mice, an extensive delay in tumor growth was observed. These data show that the artificial anginex gene can be used to produce a recombinant protein with similar activity as its synthetic counterpart and that the gene can be applied in gene therapy approaches for cancer treatment.

Original languageEnglish (US)
Pages (from-to)1073-1078
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume349
Issue number3
DOIs
StatePublished - Oct 27 2006

Bibliographical note

Funding Information:
This study was supported by a generous research grant from the Technology Foundation STW, applied science division of NOW, and the technology program of the Ministry of Economic Affairs (MPG 5465 to A.W.G.).

Keywords

  • Angiogenesis
  • Endothelial cells
  • Gene therapy
  • Recombinant anginex
  • Tumor inhibition

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