The first but not the second thrombospondin type 1 repeat of ADAMTS5 functions as an angiogenesis inhibitor

Soheila Sharghi-Namini, Huapeng Fan, K Sulochana, Padma Potturi, Wei Xiang, Yap-Seng Chong, Zhengyuan Wang, He Yang, Ruowen Ge

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)215 - 219
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume371
Issue number2
DOIs
Publication statusPublished - 2008
Externally publishedYes

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