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VEGF(121)b, a new member of the VEGF(xxx)b family of VEGF-A splice isoforms, inhibits neovascularisation and tumour growth in vivo

British journal of cancer, 2009-10, Vol.101 (7), p.1183 [Tạp chí có phản biện]

EISSN: 1532-1827 ;DOI: 10.1038/sj.bjc.6605249 ;PMID: 19707198

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Nhan đề:
VEGF(121)b, a new member of the VEGF(xxx)b family of VEGF-A splice isoforms, inhibits neovascularisation and tumour growth in vivo
Tác giả: Rennel, E S ; Varey, A H R ; Churchill, A J ; Wheatley, E R ; Stewart, L ; Mather, S ; Bates, D O ; Harper, S J
Chủ đề: Aged ; Aged, 80 and over ; Alternative Splicing ; Animals ; Apoptosis ; Cell Line, Tumor ; Cell Movement ; Colon - chemistry ; Colonic Neoplasms - chemistry ; Endothelial Cells - physiology ; Female ; Humans ; Male ; Mice ; Middle Aged ; Neoplasms - pathology ; Neoplasms - prevention & control ; Neovascularization, Pathologic - prevention & control ; Protein Isoforms ; Tissue Distribution ; Vascular Endothelial Growth Factor A - pharmacokinetics ; Vascular Endothelial Growth Factor A - physiology
Là 1 phần của: British journal of cancer, 2009-10, Vol.101 (7), p.1183
Mô tả: The key mediator of new vessel formation in cancer and other diseases is VEGF-A. VEGF-A exists as alternatively spliced isoforms - the pro-angiogenic VEGF(xxx) family generated by exon 8 proximal splicing, and a sister family, termed VEGF(xxx)b, exemplified by VEGF(165)b, generated by distal splicing of exon 8. However, it is unknown whether this anti-angiogenic property of VEGF(165)b is a general property of the VEGF(xxx)b family of isoforms. The mRNA and protein expression of VEGF(121)b was studied in human tissue. The effect of VEGF(121)b was analysed by saturation binding to VEGF receptors, endothelial migration, apoptosis, xenograft tumour growth, pre-retinal neovascularisation and imaging of biodistribution in tumour-bearing mice with radioactive VEGF(121)b. The existence of VEGF(121)b was confirmed in normal human tissues. VEGF(121)b binds both VEGF receptors with similar affinity as other VEGF isoforms, but inhibits endothelial cell migration and is cytoprotective to endothelial cells through VEGFR-2 activation. Administration of VEGF(121)b normalised retinal vasculature by reducing both angiogenesis and ischaemia. VEGF(121)b reduced the growth of xenografted human colon tumours in association with reduced microvascular density, and an intravenous bolus of VEGF(121)b is taken up into colon tumour xenografts. Here we identify a second member of the family, VEGF(121)b, with similar properties to those of VEGF(165)b, and underline the importance of the six amino acids of exon 8b in the anti-angiogenic activity of the VEGF(xxx)b isoforms.
Nơi xuất bản: England
Ngôn ngữ: English
Số nhận dạng: EISSN: 1532-1827
DOI: 10.1038/sj.bjc.6605249
PMID: 19707198
Nguồn: GFMER Free Medical Journals
MEDLINE
PubMed Central
ProQuest Central

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