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

Abstract

Capillary morphogenesis gene2 (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 tumour‑related 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 invitro, exvivo and invivo 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 invitro tubule formation and exvivo angiogenesis. One of the polypeptides, LG20, showed an inhibitory effect on invivo tumour growth of cancer cells which were co-inoculated with the vascular endothelial cells. CMG2 is a potential target for treating tumour‑related angiogenesis. The polypeptides based on the CMG2 vWA domain can potently inhibit invitro and exvivo angiogenesis, which may contribute to the inhibitory effect on invivo 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.