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.