This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Horiuchi, K.
Right arrow Articles by Blobel, C. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Horiuchi, K.
Right arrow Articles by Blobel, C. P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2003, p. 5614-5624, Vol. 23, No. 16
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.16.5614-5624.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Potential Role for ADAM15 in Pathological Neovascularization in Mice

Keisuke Horiuchi,1 Gisela Weskamp,1 Lawrence Lum,1 Hans-Peter Hammes,2 Hui Cai,1,3 Thomas A. Brodie,4 Thomas Ludwig,5 Riccardo Chiusaroli,6 Roland Baron,6 Klaus T. Preissner,7 Katia Manova,8 and Carl P. Blobel1*

Cellular Biochemistry and Biophysics Program,1 Molecular Cytology Core Facility, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center,8 Cell Biology and Molecular Biology Program, Weill Graduate School of Medical Science of Cornell University, New York, New York 10021,3 Department of Medicine, University of Heidelberg, 68167 Mannheim,2 Department of Biochemistry, Justus-Liebig University, D-35385 Giessen, Germany,7 Department of Pathology, GlaxoSmithKline, Research Triangle Park, North Carolina 27709,4 Department of Anatomy and Cell Biology and Institute of Cancer Genetics, Columbia University, New York, New York 10032,5 Department of Orthopaedics and Cell Biology, Yale University School of Medicine, New Haven, Connecticut 065106

Received 13 March 2003/ Returned for modification 22 April 2003/ Accepted 19 May 2003

ADAM15 (named for a disintegrin and metalloprotease 15, metargidin) is a membrane-anchored glycoprotein that has been implicated in cell-cell or cell-matrix interactions and in the proteolysis of molecules on the cell surface or extracellular matrix. To characterize the potential roles of ADAM15 during development and in adult mice, we analyzed its expression pattern by mRNA in situ hybridization and generated mice carrying a targeted deletion of ADAM15 (adam15-/- mice). A high level of expression of ADAM15 was found in vascular cells, the endocardium, hypertrophic cells in developing bone, and specific areas of the hippocampus and cerebellum. However, despite the pronounced expression of ADAM15 in these tissues, no major developmental defects or pathological phenotypes were evident in adam15-/- mice. The elevated levels of ADAM15 in endothelial cells prompted an evaluation of its role in neovascularization. In a mouse model for retinopathy of prematurity, adam15-/- mice had a major reduction in neovascularization compared to wild-type controls. Furthermore, the size of tumors resulting from implanted B16F0 mouse melanoma cells was significantly smaller in adam15-/- mice than in wild-type controls. Since ADAM15 does not appear to be required for developmental angiogenesis or for adult homeostasis, it may represent a novel target for the design of inhibitors of pathological neovascularization.

* Corresponding author. Mailing address: Cellular Biochemistry and Biophysics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, Box 368, 1275 York Ave., New York, NY 10021. Phone: (212) 639-2915. Fax: (212) 717-3047. E-mail: c-blobel{at}ski.mskcc.org.

Molecular and Cellular Biology, August 2003, p. 5614-5624, Vol. 23, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.16.5614-5624.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Franzke, C.-W., Bruckner-Tuderman, L., Blobel, C. P. (2009). Shedding of Collagen XVII/BP180 in Skin Depends on Both ADAM10 and ADAM9. J. Biol. Chem. 284: 23386-23396 [Abstract] [Full Text]  
  • Guaiquil, V., Swendeman, S., Yoshida, T., Chavala, S., Campochiaro, P. A., Blobel, C. P. (2009). ADAM9 Is Involved in Pathological Retinal Neovascularization. Mol. Cell. Biol. 29: 2694-2703 [Abstract] [Full Text]  
  • Tousseyn, T., Thathiah, A., Jorissen, E., Raemaekers, T., Konietzko, U., Reiss, K., Maes, E., Snellinx, A., Serneels, L., Nyabi, O., Annaert, W., Saftig, P., Hartmann, D., De Strooper, B. (2009). ADAM10, the Rate-limiting Protease of Regulated Intramembrane Proteolysis of Notch and Other Proteins, Is Processed by ADAMS-9, ADAMS-15, and the {gamma}-Secretase. J. Biol. Chem. 284: 11738-11747 [Abstract] [Full Text]  
  • Duffy, M. J., McKiernan, E., O'Donovan, N., McGowan, P. M. (2009). Role of ADAMs in Cancer Formation and Progression. Clin. Cancer Res. 15: 1140-1144 [Abstract] [Full Text]  
  • Xie, B., Shen, J., Dong, A., Swaim, M., Hackett, S. F., Wyder, L., Worpenberg, S., Barbieri, S., Campochiaro, P. A. (2008). An Adam15 amplification loop promotes vascular endothelial growth factor-induced ocular neovascularization. FASEB J. 22: 2775-2783 [Abstract] [Full Text]  
  • van Hinsbergh, V. W.M., Koolwijk, P. (2008). Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead. Cardiovasc Res 78: 203-212 [Abstract] [Full Text]  
  • Charrier-Hisamuddin, L., Laboisse, C. L., Merlin, D. (2008). ADAM-15: a metalloprotease that mediates inflammation. FASEB J. 22: 641-653 [Abstract] [Full Text]  
  • Zhong, J. L., Poghosyan, Z., Pennington, C. J., Scott, X., Handsley, M. M., Warn, A., Gavrilovic, J., Honert, K., Kruger, A., Span, P. N., Sweep, F. C.G.J., Edwards, D. R. (2008). Distinct Functions of Natural ADAM-15 Cytoplasmic Domain Variants in Human Mammary Carcinoma. Mol Cancer Res 6: 383-394 [Abstract] [Full Text]  
  • Najy, A. J., Day, K. C., Day, M. L. (2008). ADAM15 Supports Prostate Cancer Metastasis by Modulating Tumor Cell-Endothelial Cell Interaction. Cancer Res. 68: 1092-1099 [Abstract] [Full Text]  
  • Harris, L. K., Aplin, J. D. (2007). Vascular Remodeling and Extracellular Matrix Breakdown in the Uterine Spiral Arteries During Pregnancy. Reproductive Sciences 14: 28-34 [Abstract]  
  • Findley, C. M., Cudmore, M. J., Ahmed, A., Kontos, C. D. (2007). VEGF Induces Tie2 Shedding via a Phosphoinositide 3-Kinase/Akt Dependent Pathway to Modulate Tie2 Signaling. Arterioscler. Thromb. Vasc. Bio. 27: 2619-2626 [Abstract] [Full Text]  
  • Sithu, S. D., English, W. R., Olson, P., Krubasik, D., Baker, A. H., Murphy, G., D'Souza, S. E. (2007). Membrane-type 1-Matrix Metalloproteinase Regulates Intracellular Adhesion Molecule-1 (ICAM-1)-mediated Monocyte Transmigration. J. Biol. Chem. 282: 25010-25019 [Abstract] [Full Text]  
  • McGowan, P. M., Ryan, B. M., Hill, A. D.K., McDermott, E., O'Higgins, N., Duffy, M. J. (2007). ADAM-17 Expression in Breast Cancer Correlates with Variables of Tumor Progression. Clin. Cancer Res. 13: 2335-2343 [Abstract] [Full Text]  
  • Kawaguchi, N., Horiuchi, K., Becherer, J. D., Toyama, Y., Besmer, P., Blobel, C. P. (2007). Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19. J. Cell Sci. 120: 943-952 [Abstract] [Full Text]  
  • Cummins, P. M., von Offenberg Sweeney, N., Killeen, M. T., Birney, Y. A., Redmond, E. M., Cahill, P. A. (2007). Cyclic strain-mediated matrix metalloproteinase regulation within the vascular endothelium: a force to be reckoned with. Am. J. Physiol. Heart Circ. Physiol. 292: H28-H42 [Abstract] [Full Text]  
  • Saunders, W. B., Bohnsack, B. L., Faske, J. B., Anthis, N. J., Bayless, K. J., Hirschi, K. K., Davis, G. E. (2006). Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. JCB 175: 179-191 [Abstract] [Full Text]  
  • Reiss, K., Maretzky, T., Haas, I. G., Schulte, M., Ludwig, A., Frank, M., Saftig, P. (2006). Regulated ADAM10-dependent Ectodomain Shedding of {gamma}-Protocadherin C3 Modulates Cell-Cell Adhesion. J. Biol. Chem. 281: 21735-21744 [Abstract] [Full Text]  
  • Gooz, M., Gooz, P., Luttrell, L. M., Raymond, J. R. (2006). 5-HT2A Receptor Induces ERK Phosphorylation and Proliferation through ADAM-17 Tumor Necrosis Factor-{alpha}-converting Enzyme (TACE) Activation and Heparin-bound Epidermal Growth Factor-like Growth Factor (HB-EGF) Shedding in Mesangial Cells. J. Biol. Chem. 281: 21004-21012 [Abstract] [Full Text]  
  • Ohtsu, H., Dempsey, P. J., Eguchi, S. (2006). ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. Am. J. Physiol. Cell Physiol. 291: C1-C10 [Abstract] [Full Text]  
  • Davis, G. E., Senger, D. R. (2005). Endothelial Extracellular Matrix: Biosynthesis, Remodeling, and Functions During Vascular Morphogenesis and Neovessel Stabilization. Circ. Res. 97: 1093-1107 [Abstract] [Full Text]  
  • Maretzky, T., Schulte, M., Ludwig, A., Rose-John, S., Blobel, C., Hartmann, D., Altevogt, P., Saftig, P., Reiss, K. (2005). L1 Is Sequentially Processed by Two Differently Activated Metalloproteases and Presenilin/{gamma}-Secretase and Regulates Neural Cell Adhesion, Cell Migration, and Neurite Outgrowth. Mol. Cell. Biol. 25: 9040-9053 [Abstract] [Full Text]  
  • Maretzky, T., Reiss, K., Ludwig, A., Buchholz, J., Scholz, F., Proksch, E., de Strooper, B., Hartmann, D., Saftig, P. (2005). ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and {beta}-catenin translocation. Proc. Natl. Acad. Sci. USA 102: 9182-9187 [Abstract] [Full Text]  
  • Korn, R., Rohrig, S., Schulze-Kremer, S., Brinkmann, U. (2005). Common denominator procedure: a novel approach to gene-expression data mining for identification of phenotype-specific genes. Bioinformatics 21: 2766-2772 [Abstract] [Full Text]  
  • Trochon-Joseph, V., Martel-Renoir, D., Mir, L. M., Thomaidis, A., Opolon, P., Connault, E., Li, H., Grenet, C., Fauvel-Lafeve, F., Soria, J., Legrand, C., Soria, C., Perricaudet, M., Lu, H. (2004). Evidence of Antiangiogenic and Antimetastatic Activities of the Recombinant Disintegrin Domain of Metargidin. Cancer Res. 64: 2062-2069 [Abstract] [Full Text]  
  • Sahin, U., Weskamp, G., Kelly, K., Zhou, H.-M., Higashiyama, S., Peschon, J., Hartmann, D., Saftig, P., Blobel, C. P. (2004). Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands. JCB 164: 769-779 [Abstract] [Full Text]  
  • Zhou, H.-M., Weskamp, G., Chesneau, V., Sahin, U., Vortkamp, A., Horiuchi, K., Chiusaroli, R., Hahn, R., Wilkes, D., Fisher, P., Baron, R., Manova, K., Basson, C. T., Hempstead, B., Blobel, C. P. (2004). Essential Role for ADAM19 in Cardiovascular Morphogenesis. Mol. Cell. Biol. 24: 96-104 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»