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Molecular and Cellular Biochemistry

, Volume 375, Issue 1–2, pp 207–217 | Cite as

Matriptase-2 inhibits HECV motility and tubule formation in vitro and tumour angiogenesis in vivo

  • Siobhan L. Webb
  • Andrew J. Sanders
  • Malcolm D. Mason
  • Wen G. JiangEmail author
Article
  • 395 Downloads

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). HECVmat2 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.

Keywords

Matriptase-2 TTSP Angiogenesis Prostate cancer uPA 

Notes

Acknowledgments

The authors wish to thank Cancer Research Wales for supporting this study.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Siobhan L. Webb
    • 1
  • Andrew J. Sanders
    • 1
  • Malcolm D. Mason
    • 1
  • Wen G. Jiang
    • 1
    Email author
  1. 1.Metastasis & Angiogenesis Research Group, Institute of Cancer and GeneticsCardiff University School of MedicineCardiffUK

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