title: Matriptase-2 inhibits HECV motility and tubule formation in vitro and tumour angiogenesis in vivo.
abstract: The type II transmembrane serine proteases (TTSP) are cell surface proteolytic enzymes that mediate a diverse range of cellular functions, including tumour invasion and metastasis. Matriptase-2 is a member of the TTSP family and has been shown to have a key role in cancer progression. The role of matriptase-2 in angiogenesis and angiogenesis-related cancer progression is currently poorly understood. This study aims to elucidate the role of matriptase-2 in tumour angiogenesis. Matriptase-2 was over-expressed in human vascular endothelial cells, HECV, using a mammalian expression plasmid. The altered cells were used in a number of in vitro and in vivo assays designed to investigate the involvement of matriptase-2 in angiogenesis. Over-expression had no significant effect on the growth and adhesion of HECV cells. However, there was a significant reduction in the motility of the cells and their ability to form tubules in an artificial basement membrane (p < 0.01 for both). HECV(mat2 exp) cells inoculated into CD-1 athymic mice along with either PC-3 prostate cancer cells or MDA-MB-231 breast cancer cells showed a dramatic decrease in tumour development and growth in the prostate tumours (p < 0.01) and a lesser, non-significant, decrease in the breast tumours (p = 0.08). Over-expression of matriptase-2 also decreased urokinase type plasminogen activator total protein levels in HECV and prostate cells. The study concludes that matriptase-2 has the ability to suppress the angiogenic nature of HECV cells in vitro and in vivo. It also suggests that matriptase-2 could have a potential role in prostate and breast tumour suppression through its anti-angiogenic properties.
authors.affiliation: Metastasis & Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: Siobhan L
authors.initials: SL
authors.lastname: Webb
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sanders
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology*; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D012697:Serine Endopeptidases; C467801:matriptase 2; D014568:Urokinase-Type Plasminogen Activator