Therapeutic potential of capillary morphogenesis gene 2 extracellular vWA domain in tumour-related angiogenesis

Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409, Sun, Ping-Hui, Sanders, Andrew James ORCID: https://orcid.org/0000-0002-7997-5286, Martin, Tracey Amanda ORCID: https://orcid.org/0000-0003-2690-4908, Lane, Jane ORCID: https://orcid.org/0000-0002-1926-4909, Mason, Malcolm David ORCID: https://orcid.org/0000-0003-1505-2869 and Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 2014. Therapeutic potential of capillary morphogenesis gene 2 extracellular vWA domain in tumour-related angiogenesis. International Journal of Oncology 45 (4) , pp. 1565-1573. 10.3892/ijo.2014.2533

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Abstract

Capillary morphogenesis gene 2 (CMG2) is a receptor of anthrax toxin and plays an important role in angiogenesis. It has been shown to be involved in the cell adhesion and motility of various cell types, including epithelia and endothelia. The present study aimed to examine the therapeutic potential of targeting CMG2 to prevent tumourrelated new vasculature. The full-length coding sequence of the human CMG2 gene and different fragments of the CMG2 vWA domain were amplified and constructed into a mammalian expression plasmid vector. The effect of CMG2 and its vWA domain on endothelial cells and angiogenesis was assessed using relevant in vitro, ex vivo and in vivo models. The overexpression of CMG2 enhanced the adhesion of endothelial cells to extracellular matrix, but was negatively associated with cell migration. Overexpression of CMG2 and the vWA domain fragments inhibited the tubule formation and migration of endothelial cells. Small peptides based on the amino acid sequence of the CMG2 vWA domain fragments potently inhibited in vitro tubule formation and ex vivo angiogenesis. One of the polypeptides, LG20, showed an inhibitory effect on in vivo tumour growth of cancer cells which were co-inoculated with the vascular endothelial cells. CMG2 is a potential target for treating tumourrelated angiogenesis. The polypeptides based on the CMG2 vWA domain can potently inhibit in vitro and ex vivo angiogenesis, which may contribute to the inhibitory effect on in vivo tumour growth. Further investigations are required to shed light on the machinery and may provide a novel therapeutic approach for inhibition of angiogenesis in cancer management.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Spandidos Publications
ISSN:	1019-6439
Last Modified:	07 Feb 2023 02:22
URI:	https://orca.cardiff.ac.uk/id/eprint/75779

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