Document Detail


ADAM8 is a negative regulator of retinal neovascularization and of the growth of heterotopically injected tumor cells in mice.
MedLine Citation:
PMID:  20119708     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ADAM8 is a member of the "a disintegrin and metalloproteinase" (ADAM) family of membrane-anchored metalloproteinases. ADAM8-deficient mice have no evident spontaneous developmental or pathological defects, and little is currently known about the role of ADAM8 in disease. Here, we investigated the contribution of ADAM8 to pathological neovascularization in mice using an oxygen-induced retinopathy (OIR) model and heterotopical injection of tumor cells. We found an increase in retinal re-vascularization but fewer neovascular tufts in the OIR model and increased growth of heterotopically injected tumor cells in Adam8-/- mice compared with wild-type controls. These results suggest that ADAM8 functions to limit both of these processes in wild-type mice. In cell-based assays, overexpression of ADAM8 increased the ectodomain shedding of several co-expressed membrane proteins with roles in angiogenesis (CD31, Tie-2, Flk-1, Flt-1, EphrinB2, EphB4, VE-cadherin, KL-1, E-selectin, and neuregulin-1beta2). Thus, dysregulated expression of ADAM8 in endothelial cells in vivo could potentially increase the processing of these and other substrate proteins. Taken together, our findings suggest that inhibiting ADAM8 could be useful for promoting re-vascularization and thereby preventing formation of neovascular tufts in proliferative retinopathies. On the other hand, blocking ADAM8 could be detrimental in the context of rapidly growing tumors.
Authors:
Victor H Guaiquil; Steven Swendeman; Wenhui Zhou; Patricio Guaiquil; Gisela Weskamp; Jörg W Bartsch; Carl P Blobel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-01-30
Journal Detail:
Title:  Journal of molecular medicine (Berlin, Germany)     Volume:  88     ISSN:  1432-1440     ISO Abbreviation:  J. Mol. Med.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-26     Completed Date:  2010-07-15     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  9504370     Medline TA:  J Mol Med (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  497-505     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / genetics,  metabolism*
Animals
Antigens, CD / genetics,  metabolism*
Cell Line
Endothelial Cells / metabolism,  pathology
Gene Deletion
Melanoma / metabolism*,  pathology
Membrane Proteins / genetics,  metabolism*
Mice
Mice, Inbred C57BL
Retina / cytology,  pathology*
Retinal Neovascularization / metabolism*
Up-Regulation
Grant Support
ID/Acronym/Agency:
EY015758/EY/NEI NIH HHS; R01 EY015719/EY/NEI NIH HHS; R01 EY015719-06/EY/NEI NIH HHS; R01 EY015719-06S1/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Membrane Proteins; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/Adam8 protein, mouse
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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