TY - JOUR
T1 - The first but not the second thrombospondin type 1 repeat of ADAMTS5 functions as an angiogenesis inhibitor
AU - Sharghi-Namini, Soheila
AU - Fan, Huapeng
AU - Sulochana, K
AU - Potturi, Padma
AU - Xiang, Wei
AU - Chong, Yap-Seng
AU - Wang, Zhengyuan
AU - Yang, He
AU - Ge, Ruowen
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/pubmed?term=18433719%5Buid%5D
U2 - 10.1016/j.bbrc.2008.04.047
DO - 10.1016/j.bbrc.2008.04.047
M3 - Article
SN - 0006-291X
VL - 371
SP - 215
EP - 219
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -