The first but not the second thrombospondin type 1 repeat of ADAMTS5 functions as an angiogenesis inhibitor
- Department of Biological Sciences, Faculty of Science, National University of Singapore, Block S2, Science Drive 4, Singapore 117543 (Singapore)
- Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore)
- Bioinformatics Institute, 30 Biopolis Street, Matrix 07-01, Singapore 138671 (Singapore)
Angiogenesis is critical for tumour growth and metastasis where factors that regulate this process are potential targets for development of anti-cancer drugs. In this study, we show that the first TSR domain of the extracellular matrix protease ADAMTS5, unlike the second TSR, has anti-angiogenic activities where it inhibits endothelial cell tube formation on Matrigel, reduces cell proliferation and attachment, while promoting cell apoptosis and migration, all in a dose-dependent manner. Furthermore, it influences the architecture of endothelial cells by disrupting actin stress fibres and reducing focal adhesions, likely via suppressing RhoA activation. TSR1 of ADAMTS5 is therefore a novel anti-angiogenic peptide and could serve as a prototype for future development into anti-cancer drugs.
- OSTI ID:
- 21143731
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 371, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2008.04.047; PII: S0006-291X(08)00693-1; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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