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.
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Authors | Siobhan L Webb, Andrew J Sanders, Malcolm D Mason, Wen G Jiang |
Journal | Molecular and cellular biochemistry
(Mol Cell Biochem)
Vol. 375
Issue 1-2
Pg. 207-17
(Mar 2013)
ISSN: 1573-4919 [Electronic] Netherlands |
PMID | 23238872
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Membrane Proteins
- Serine Endopeptidases
- matriptase 2
- Urokinase-Type Plasminogen Activator
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Topics |
- Animals
- Cell Adhesion
- Cell Movement
- Cell Proliferation
- Cells, Cultured
- Endothelial Cells
(physiology)
- Endothelium, Vascular
(pathology)
- Gene Expression
- Genes, Tumor Suppressor
- Humans
- Membrane Proteins
(genetics, metabolism, physiology)
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Neoplasms
(blood supply)
- Neovascularization, Pathologic
(enzymology)
- Serine Endopeptidases
(genetics, metabolism, physiology)
- Urokinase-Type Plasminogen Activator
(metabolism)
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