Anti-angiogenesis and anti-tumor activity of recombinant anginex

Journal Article · Fri Oct 27 04:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.08.154· OSTI ID:20854545

Dings, Ruud P.M. ^[1]; Linden, Edith van der ^[2]; Mayo, Kevin H ^[1]; Griffioen, Arjan W ^[2]

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1. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN (United States)
2. Angiogenesis Laboratory, Research Institute Growth and Development (GROW), Department of Pathology, Maastricht University and University Hospital, P.O. Box 5800, 6202 AZ Maastricht (Netherlands)

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.

• OSTI ID: 20854545
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 349; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL PROLIFERATION
GENE THERAPY
GENES
IN VITRO
IN VIVO
INHIBITION
MELANOMAS
MICE
PEPTIDES
SUBCUTANEOUS INJECTION