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VEGF-A splicing: the key to anti-angiogenic therapeutics?

Nature Reviews Cancer volume 8, pages 880–887 (2008)Cite this article

Abstract

The physiology of microvessels limits the growth and development of tumours. Tumours gain nutrients and excrete waste through growth-associated microvessels. New anticancer therapies target this microvasculature by inhibiting vascular endothelial growth factor A (VEGF-A) splice isoforms that promote microvessel growth. However, certain VEGF-A splice isoforms in normal tissues inhibit growth of microvessels. Thus, it is the VEGF-A isoform balance, which is controlled by mRNA splicing, that orchestrates angiogenesis. Here, we highlight the functional differences between the pro-angiogenic and the anti-angiogenic VEGF-A isoform families and the potential to harness the synthetic capacity of cancer cells to produce factors that inhibit, rather than aid, cancer growth.

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Figure 1: Protein and mRNA products of human vascular endothelial growth factor A (VEGF-A).
Figure 2: Vascular endothelial growth factor A (VEGF-A) C′ terminal splicing regulation.
Figure 3: Signalling pathways downstream of vascular endothelial growth factor (VEGF-A)xxx and VEGF-Axxxb.
Figure 4: The structure of vascular endothelial growth factor A (VEGF-A).
Figure 5: Vascular endothelial growth factor A (VEGF-A)165b and VEGF-A165 interaction with VEGF receptor 2 (VEGFR2).

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  1. Department of Physiology & Pharmacology, Steven J. Harper and David O. Bates are at the Microvascular Research Laboratories, Bristol Heart Institute, School of Veterinary Science, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK.,

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Correspondence to Steven J. Harper.

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VEGFxxxb isoforms are protected by a patent owned by the University of Bristol. The work described has been supported by the Wellcome Trust, the British Heart Foundation and the University of Bristol. D.O.B. is employed by the University of Bristol, S.J.H. by North Bristol NHS Trust, which has a revenue-sharing agreement with the University of Bristol.

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Harper, S., Bates, D. VEGF-A splicing: the key to anti-angiogenic therapeutics?. Nat Rev Cancer 8, 880–887 (2008). https://doi.org/10.1038/nrc2505

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