title: The first but not the second thrombospondin type 1 repeat of ADAMTS5 functions as an angiogenesis inhibitor.
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.
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, Block S2, Science Drive 4, Singapore 117543, Singapore.
authors.forename: Soheila
authors.initials: S
authors.lastname: Sharghi-Namini
authors.forename: Huapeng
authors.initials: H
authors.lastname: Fan
authors.forename: K N
authors.initials: KN
authors.lastname: Sulochana
authors.forename: Padma
authors.initials: P
authors.lastname: Potturi
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.forename: Yap-Seng
authors.initials: YS
authors.lastname: Chong
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Wang
authors.forename: He
authors.initials: H
authors.lastname: Yang
authors.forename: Ruowen
authors.initials: R
authors.lastname: Ge
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D000071116:ADAMTS5 Protein; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D017209:Apoptosis; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007797:Laminin / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000378:metabolism; D022502:Stress Fibers / Q000187:drug effects; D019700:Thrombospondin 1 / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D007797:Laminin; D010455:Peptides; D011509:Proteoglycans; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human