ADAM8 is a negative regulator of retinal neovascularization and of the growth of heterotopically injected tumor cells in mice Journal Article
| Authors: | Guaiquil, V. H.; Swendeman, S.; Zhou, W.; Guaiquil, P.; Weskamp, G.; Bartsch, J. W.; Blobel, C. P. |
| Article Title: | ADAM8 is a negative regulator of retinal neovascularization and of the growth of heterotopically injected tumor cells in mice |
| Abstract: | 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 wildtype 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, Eselectin, and neuregulin-1β2). 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. © Springer-Verlag 2010. |
| Keywords: | controlled study; protein expression; unclassified drug; gene deletion; pathogenesis; nonhuman; protein function; animal cell; mouse; animals; mice; animal tissue; melanoma; cell growth; cell line; animal experiment; animal model; membrane proteins; in vivo study; enzyme activity; vasculotropin receptor 2; angiogenesis; mice, inbred c57bl; hypoxia; endothelium cell; endothelial cells; protein processing; membrane protein; tumor cell; melanoma cell; retina; antigens, cd; up-regulation; angiopoietin receptor; vasculotropin receptor 1; endothelial leukocyte adhesion molecule 1; metalloproteinase; adam proteins; cd31 antigen; vascular endothelial cadherin; adam8; oxygen-induced retinopathy; pathological neovascularization; proliferative retinopathy; protein ectodomain shedding; ephrin b2; ephrin b4; neuregulin 1beta2; protein adam8; protein kl 1; retina neovascularization; retinal neovascularization |
| Journal Title: | Journal of Molecular Medicine |
| Volume: | 88 |
| Issue: | 5 |
| ISSN: | 0946-2716 |
| Publisher: | Springer |
| Date Published: | 2010-05-01 |
| Start Page: | 497 |
| End Page: | 505 |
| Language: | English |
| DOI: | 10.1007/s00109-010-0591-8 |
| PUBMED: | 20119708 |
| PROVIDER: | scopus |
| PMCID: | PMC2862722 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: JMLME" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work