title: Therapeutic potential of capillary morphogenesis gene 2 extracellular vWA domain in tumour‑related angiogenesis.
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 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 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 tumour‑related 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.
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University-Peking University Cancer Institute, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University-Peking University Cancer Institute, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Ping-Hui
authors.initials: PH
authors.lastname: Sun
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University-Peking University Cancer Institute, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sanders
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University-Peking University Cancer Institute, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University-Peking University Cancer Institute, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Lane
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University-Peking University Cancer Institute, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University-Peking University Cancer Institute, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D018000:Receptors, Peptide / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D014841:von Willebrand Factor / Q000737:chemistry
chemical_list: C447150:ANTXR2 protein, human; D000970:Antineoplastic Agents; D010455:Peptides; D018000:Receptors, Peptide; D014841:von Willebrand Factor