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Angiogenesis

Cutting off growth

Nature Reviews Cancer volume 3, page 633 (2003)Cite this article

The DNAzymes that had been engineered to target human EGR1 mRNA inhibited endothelial-cell migration in an in vitro assay and inhibited capillary tubule formation by endothelial cells cultured on basement-membrane matrices (Matrigel). Blood-vessel formation within Matrigel plugs that had been injected subcutaneously into mice was also blocked by a mouse Egr1 DNAzyme (ED5). Use of a control DNAzyme — with a scrambled hybridization sequence — had no effect in any of these experiments.

ED5 can therefore inhibit angiogenesis, but what effect does this inhibition have on tumour growth? When ED5 was administered subcutaneously to BALB/c nude mice that had been injected with MCF-7 breast cancer cells, a fivefold reduction in tumour size was seen compared with mice injected with a scrambled DNAzyme or vehicle alone. ED5 had no direct inhibitory effect on MCF-7 proliferation; it decreased vascular density in the tumours. Local intratumoral injection also blocked MCF-7 tumour growth. Importantly, no systemic side effects, on wound healing, haemostasis or reproduction were seen.

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ORIGINAL RESEARCH PAPER

  1. Fahmy, R. G. et al. Transcription factor Egr-1 supports FGF-dependent angiogenesis during neovascularization and tumour growth. Nature Med. 9, 1026–1032 (2003)

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Authors
  1. Ezzie Hutchinson
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Hutchinson, E. Cutting off growth. Nat Rev Cancer 3, 633 (2003). https://doi.org/10.1038/nrc1179

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  • DOI: https://doi.org/10.1038/nrc1179

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