|  Help  |  About  |  Contact Us

Publication : ADAMTS9 is a cell-autonomously acting, anti-angiogenic metalloprotease expressed by microvascular endothelial cells.

First Author  Koo BH Year  2010
Journal  Am J Pathol Volume  176
Issue  3 Pages  1494-504
PubMed ID  20093484 Mgi Jnum  J:156090
Mgi Id  MGI:4418720 Doi  10.2353/ajpath.2010.090655
Citation  Koo BH, et al. (2010) ADAMTS9 Is a Cell-Autonomously Acting,Anti-Angiogenic Metalloprotease Expressed by Microvascular Endothelial Cells. Am J Pathol 176(3):1494-504
abstractText  The metalloprotease ADAMTS9 participates in melanoblast development and is a tumor suppressor in esophageal and nasopharyngeal cancer. ADAMTS9 null mice die before gastrulation, but, ADAMTS9(+/-) mice were initially thought to be normal. However, when congenic with the C57Bl/6 strain, 80% of ADAMTS9(+/-) mice developed spontaneous corneal neovascularization. beta-Galactosidase staining enabled by a lacZ cassette targeted to the ADAMTS9 locus showed that capillary endothelial cells (ECs) in embryonic and adult tissues and in capillaries growing into heterotopic tumors expressed ADAMTS9. Heterotopic B.16-F10 melanomas elicited greater vascular induction in ADAMTS9(+/-) mice than in wild-type littermates, suggesting a potential inhibitory role in tumor angiogenesis. Treatment of cultured human microvascular ECs with ADAMTS9 small-interfering RNA resulted in enhanced filopodial extension, decreased cell adhesion, increased cell migration, and enhanced formation of tube-like structures on Matrigel. Conversely, overexpression of catalytically active, but not inactive, ADAMTS9 in ECs led to fewer tube-like structures, demonstrating that the proteolytic activity of ADAMTS9 was essential. However, unlike the related metalloprotease ADAMTS1, which exerts anti-angiogenic effects by cleavage of thrombospondins and sequestration of vascular endothelial growth factor165, ADAMTS9 neither cleaved thrombospondins 1 and 2, nor bound vascular endothelial growth factor165. Taken together, these data identify ADAMTS9 as a novel, constitutive, endogenous angiogenesis inhibitor that operates cell-autonomously in ECs via molecular mechanisms that are distinct from those used by ADAMTS1.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

7 Bio Entities

0 Expression