Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text PDF (Full Text) PPT slides of all figures Correction (v155,p1359) Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mechtersheimer, S. Articles by Altevogt, P. Search for Related Content PubMed PubMed Citation Articles by Mechtersheimer, S. Articles by Altevogt, P. Social Bookmarking                      What's this?

¹ Tumor Immunology Program, G0100, German Cancer Research Center, D-69120 Heidelberg, Germany
² Department of Pathology, Kaplan Hospital, Rehovot 76100, Israel
³ Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106
⁴ Institute of Biochemistry, University of Mainz, D-55128 Mainz, Germany

Address correspondence to Peter Altevogt, Tumor Immunology Program, G0100, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Tel.: 49-6221-423-714. Fax: 49-6221-423-702. E-mail: p.altevogt{at}dkfz-heidelberg.de

The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to vß5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by vß5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via vß5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions.

Key Words: L1; shedding; ADAM10; cell migration; integrins

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Gouveia, R. M., Gomes, C. M., Sousa, M., Alves, P. M., Costa, J. (2008). Kinetic Analysis of L1 Homophilic Interaction: ROLE OF THE FIRST FOUR IMMUNOGLOBULIN DOMAINS AND IMPLICATIONS ON BINDING MECHANISM. J. Biol. Chem. 283: 28038-28047 [Abstract] [Full Text]  
• Ponnuchamy, B., Khalil, R. A. (2008). Role of ADAMs in Endothelial Cell Permeability: Cadherin Shedding and Leukocyte Rolling. Circ. Res. 102: 1139-1142 [Full Text]  
• Finas, D., Huszar, M., Agic, A., Dogan, S., Kiefel, H., Riedle, S., Gast, D., Marcovich, R., Noack, F., Altevogt, P., Fogel, M., Hornung, D. (2008). L1 cell adhesion molecule (L1CAM) as a pathogenetic factor in endometriosis. Hum Reprod 23: 1053-1062 [Abstract] [Full Text]  
• Zecchini, S., Bianchi, M., Colombo, N., Fasani, R., Goisis, G., Casadio, C., Viale, G., Liu, J., Herlyn, M., Godwin, A. K., Nuciforo, P. G., Cavallaro, U. (2008). The Differential Role of L1 in Ovarian Carcinoma and Normal Ovarian Surface Epithelium. Cancer Res. 68: 1110-1118 [Abstract] [Full Text]  
• Buhusi, M., Schlatter, M. C., Demyanenko, G. P., Thresher, R., Maness, P. F. (2008). L1 Interaction with Ankyrin Regulates Mediolateral Topography in the Retinocollicular Projection. J. Neurosci. 28: 177-188 [Abstract] [Full Text]  
• Wolman, M. A., Regnery, A. M., Becker, T., Becker, C. G., Halloran, M. C. (2007). Semaphorin3D Regulates Axon Axon Interactions by Modulating Levels of L1 Cell Adhesion Molecule. J. Neurosci. 27: 9653-9663 [Abstract] [Full Text]  
• Gavert, N., Sheffer, M., Raveh, S., Spaderna, S., Shtutman, M., Brabletz, T., Barany, F., Paty, P., Notterman, D., Domany, E., Ben-Ze'ev, A. (2007). Expression of L1-CAM and ADAM10 in Human Colon Cancer Cells Induces Metastasis. Cancer Res. 67: 7703-7712 [Abstract] [Full Text]  
• Boo, Y.-J., Park, J.-M., Kim, J., Chae, Y.-S., Min, B.-W., Um, J.-W., Moon, H.-Y. (2007). L1 Expression as a Marker for Poor Prognosis, Tumor Progression, and Short Survival in Patients with Colorectal Cancer. Ann. Surg. Oncol. 14: 1703-1711 [Abstract] [Full Text]  
• Zhang, Y., Klassen, H. J., Tucker, B. A., Perez, M.-T. R., Young, M. J. (2007). CNS Progenitor Cells Promote a Permissive Environment for Neurite Outgrowth via a Matrix Metalloproteinase-2-Dependent Mechanism. J. Neurosci. 27: 4499-4506 [Abstract] [Full Text]  
• Knogler, K., Grunberg, J., Zimmermann, K., Cohrs, S., Honer, M., Ametamey, S., Altevogt, P., Fogel, M., Schubiger, P. A., Novak-Hofer, I. (2007). Copper-67 Radioimmunotherapy and Growth Inhibition by Anti-L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis. Clin. Cancer Res. 13: 603-611 [Abstract] [Full Text]  
• Shtutman, M., Levina, E., Ohouo, P., Baig, M., Roninson, I. B. (2006). Cell Adhesion Molecule L1 Disrupts E-Cadherin-Containing Adherens Junctions and Increases Scattering and Motility of MCF7 Breast Carcinoma Cells. Cancer Res. 66: 11370-11380 [Abstract] [Full Text]  
• Arlt, M. J.E., Novak-Hofer, I., Gast, D., Gschwend, V., Moldenhauer, G., Grunberg, J., Honer, M., Schubiger, P. A., Altevogt, P., Kruger, A. (2006). Efficient Inhibition of Intra-Peritoneal Tumor Growth and Dissemination of Human Ovarian Carcinoma Cells in Nude Mice by Anti-L1-Cell Adhesion Molecule Monoclonal Antibody Treatment. Cancer Res. 66: 936-943 [Abstract] [Full Text]  
• Conacci-Sorrell, M., Kaplan, A., Raveh, S., Gavert, N., Sakurai, T., Ben-Ze'ev, A. (2005). The Shed Ectodomain of Nr-CAM Stimulates Cell Proliferation and Motility, and Confers Cell Transformation. Cancer Res. 65: 11605-11612 [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]  
• Huang, J., Bridges, L. C., White, J. M. (2005). Selective Modulation of Integrin-mediated Cell Migration by Distinct ADAM Family Members. Mol. Biol. Cell 16: 4982-4991 [Abstract] [Full Text]  
• Hehr, C. L., Hocking, J. C., McFarlane, S. (2005). Matrix metalloproteinases are required for retinal ganglion cell axon guidance at select decision points. Development 132: 3371-3379 [Abstract] [Full Text]  
• Gutwein, P., Stoeck, A., Riedle, S., Gast, D., Runz, S., Condon, T. P., Marme, A., Phong, M.-C., Linderkamp, O., Skorokhod, A., Altevogt, P. (2005). Cleavage of L1 in Exosomes and Apoptotic Membrane Vesicles Released from Ovarian Carcinoma Cells. Clin. Cancer Res. 11: 2492-2501 [Abstract] [Full Text]  
• Gavert, N., Conacci-Sorrell, M., Gast, D., Schneider, A., Altevogt, P., Brabletz, T., Ben-Ze'ev, A. (2005). L1, a novel target of {beta}-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J. Cell Biol. 168: 633-642 [Abstract] [Full Text]  
• Suzuki, T, Izumoto, S, Fujimoto, Y, Maruno, M, Ito, Y, Yoshimine, T (2005). Clinicopathological study of cellular proliferation and invasion in gliomatosis cerebri: important role of neural cell adhesion molecule L1 in tumour invasion. J. Clin. Pathol. 58: 166-171 [Abstract] [Full Text]  
• Allory, Y., Matsuoka, Y., Bazille, C., Christensen, E. I., Ronco, P., Debiec, H. (2005). The L1 Cell Adhesion Molecule Is Induced in Renal Cancer Cells and Correlates with Metastasis in Clear Cell Carcinomas. Clin. Cancer Res. 11: 1190-1197 [Abstract] [Full Text]  
• Walmsley, A. R., McCombie, G., Neumann, U., Marcellin, D., Hillenbrand, R., Mir, A. K., Frentzel, S. (2004). Zinc metalloproteinase-mediated cleavage of the human Nogo-66 receptor. J. Cell Sci. 117: 4591-4602 [Abstract] [Full Text]  
• Heiz, M., Grunberg, J., Schubiger, P. A., Novak-Hofer, I. (2004). Hepatocyte Growth Factor-induced Ectodomain Shedding of Cell Adhesion Molecule L1: ROLE OF THE L1 CYTOPLASMIC DOMAIN. J. Biol. Chem. 279: 31149-31156 [Abstract] [Full Text]  
• Silletti, S., Yebra, M., Perez, B., Cirulli, V., McMahon, M., Montgomery, A. M. P. (2004). Extracellular Signal-regulated Kinase (ERK)-dependent Gene Expression Contributes to L1 Cell Adhesion Molecule-dependent Motility and Invasion. J. Biol. Chem. 279: 28880-28888 [Abstract] [Full Text]  
• Ohnishi, H., Kobayashi, H., Okazawa, H., Ohe, Y., Tomizawa, K., Sato, R., Matozaki, T. (2004). Ectodomain Shedding of SHPS-1 and Its Role in Regulation of Cell Migration. J. Biol. Chem. 279: 27878-27887 [Abstract] [Full Text]  
• Abel, S., Hundhausen, C., Mentlein, R., Schulte, A., Berkhout, T. A., Broadway, N., Hartmann, D., Sedlacek, R., Dietrich, S., Muetze, B., Schuster, B., Kallen, K.-J., Saftig, P., Rose-John, S., Ludwig, A. (2004). The Transmembrane CXC-Chemokine Ligand 16 Is Induced by IFN-{gamma} and TNF-{alpha} and Shed by the Activity of the Disintegrin-Like Metalloproteinase ADAM10. J. Immunol. 172: 6362-6372 [Abstract] [Full Text]  
• Naus, S., Richter, M., Wildeboer, D., Moss, M., Schachner, M., Bartsch, J. W. (2004). Ectodomain Shedding of the Neural Recognition Molecule CHL1 by the Metalloprotease-disintegrin ADAM8 Promotes Neurite Outgrowth and Suppresses Neuronal Cell Death. J. Biol. Chem. 279: 16083-16090 [Abstract] [Full Text]  
• Itoh, K., Cheng, L., Kamei, Y., Fushiki, S., Kamiguchi, H., Gutwein, P., Stoeck, A., Arnold, B., Altevogt, P., Lemmon, V. (2004). Brain development in mice lacking L1-L1 homophilic adhesion. J. Cell Biol. 165: 145-154 [Abstract] [Full Text]  
• Murai, T., Miyazaki, Y., Nishinakamura, H., Sugahara, K. N., Miyauchi, T., Sako, Y., Yanagida, T., Miyasaka, M. (2004). Engagement of CD44 Promotes Rac Activation and CD44 Cleavage during Tumor Cell Migration. J. Biol. Chem. 279: 4541-4550 [Abstract] [Full Text]  
• McCulloch, D. R., Akl, P., Samaratunga, H., Herington, A. C., Odorico, D. M. (2004). Expression of the Disintegrin Metalloprotease, ADAM-10, in Prostate Cancer and Its Regulation by Dihydrotestosterone, Insulin-Like Growth Factor I, and Epidermal Growth Factor in the Prostate Cancer Cell Model LNCaP. Clin. Cancer Res. 10: 314-323 [Abstract] [Full Text]  
• Alberts, P., Rudge, R., Hinners, I., Muzerelle, A., Martinez-Arca, S., Irinopoulou, T., Marthiens, V., Tooze, S., Rathjen, F., Gaspar, P., Galli, T. (2003). Cross Talk between Tetanus Neurotoxin-insensitive Vesicle-associated Membrane Protein-mediated Transport and L1-mediated Adhesion. Mol. Biol. Cell 14: 4207-4220 [Abstract] [Full Text]  
• Garton, K. J., Gough, P. J., Philalay, J., Wille, P. T., Blobel, C. P., Whitehead, R. H., Dempsey, P. J., Raines, E. W. (2003). Stimulated Shedding of Vascular Cell Adhesion Molecule 1 (VCAM-1) Is Mediated by Tumor Necrosis Factor-{alpha}-converting Enzyme (ADAM 17). J. Biol. Chem. 278: 37459-37464 [Abstract] [Full Text]  
• Walcheck, B., Alexander, S. R., St. Hill, C. A., Matala, E. (2003). ADAM-17-independent shedding of L-selectin. J. Leukoc. Biol. 74: 389-394 [Abstract] [Full Text]  
• Hundhausen, C., Misztela, D., Berkhout, T. A., Broadway, N., Saftig, P., Reiss, K., Hartmann, D., Fahrenholz, F., Postina, R., Matthews, V., Kallen, K.-J., Rose-John, S., Ludwig, A. (2003). The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood 102: 1186-1195 [Abstract] [Full Text]  
• Buhusi, M., Midkiff, B. R., Gates, A. M., Richter, M., Schachner, M., Maness, P. F. (2003). Close Homolog of L1 Is an Enhancer of Integrin-mediated Cell Migration. J. Biol. Chem. 278: 25024-25031 [Abstract] [Full Text]  
• Kiryushko, D., Kofoed, T., Skladchikova, G., Holm, A., Berezin, V., Bock, E. (2003). A Synthetic Peptide Ligand of Neural Cell Adhesion Molecule (NCAM), C3d, Promotes Neuritogenesis and Synaptogenesis and Modulates Presynaptic Function in Primary Cultures of Rat Hippocampal Neurons. J. Biol. Chem. 278: 12325-12334 [Abstract] [Full Text]  
• Kalus, I., Schnegelsberg, B., Seidah, N. G., Kleene, R., Schachner, M. (2003). The Proprotein Convertase PC5A and a Metalloprotease Are Involved in the Proteolytic Processing of the Neural Adhesion Molecule L1. J. Biol. Chem. 278: 10381-10388 [Abstract] [Full Text]  
• Hirako, Y., Yoshino, K., Zillikens, D., Owaribe, K. (2003). Extracellular Cleavage of Bullous Pemphigoid Antigen 180/Type XVII Collagen and Its Involvement in Hemidesmosomal Disassembly. J Biochem 133: 197-206 [Abstract] [Full Text]  
• Xu, Y.-Z., Ji, Y., Zipser, B., Jellies, J., Johansen, K. M., Johansen, J. (2003). Proteolytic Cleavage of the Ectodomain of the L1 CAM Family Member Tractin. J. Biol. Chem. 278: 4322-4330 [Abstract] [Full Text]  
• Demyanenko, G. P., Maness, P. F. (2003). The L1 Cell Adhesion Molecule Is Essential for Topographic Mapping of Retinal Axons. J. Neurosci. 23: 530-538 [Abstract] [Full Text]  
• Seals, D. F., Courtneidge, S. A. (2003). The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev. 17: 7-30 [Full Text]  
• Kang, T., Park, H. I., Suh, Y., Zhao, Y.-G., Tschesche, H., Sang, Q.-X. A. (2002). Autolytic Processing at Glu586-Ser587 within the Cysteine-rich Domain of Human Adamalysin 19/Disintegrin-Metalloproteinase 19 Is Necessary for Its Proteolytic Activity. J. Biol. Chem. 277: 48514-48522 [Abstract] [Full Text]  
• Grantcharova, E., Furkert, J., Reusch, H. P., Krell, H.-W., Papsdorf, G., Beyermann, M., Schulein, R., Rosenthal, W., Oksche, A. (2002). The Extracellular N Terminus of the Endothelin B (ETB) Receptor Is Cleaved by a Metalloprotease in an Agonist-dependent Process. J. Biol. Chem. 277: 43933-43941 [Abstract] [Full Text]  
• Hartmann, D., de Strooper, B., Serneels, L., Craessaerts, K., Herreman, A., Annaert, W., Umans, L., Lubke, T., Lena Illert, A., von Figura, K., Saftig, P. (2002). The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for {alpha}-secretase activity in fibroblasts. Hum Mol Genet 11: 2615-2624 [Abstract] [Full Text]  
• Hintz, K. A., Rassias, A. J., Wardwell, K., Moss, M. L., Morganelli, P. M., Pioli, P. A., Givan, A. L., Wallace, P. K., Yeager, M. P., Guyre, P. M. (2002). Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163. J. Leukoc. Biol. 72: 711-717 [Abstract] [Full Text]  
• Conacci-Sorrell, M. E., Ben-Yedidia, T., Shtutman, M., Feinstein, E., Einat, P., Ben-Ze'ev, A. (2002). Nr-CAM is a target gene of the beta -catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev. 16: 2058-2072 [Abstract] [Full Text]  
• Gaultier, A., Cousin, H., Darribere, T., Alfandari, D. (2002). ADAM13 Disintegrin and Cysteine-rich Domains Bind to the Second Heparin-binding Domain of Fibronectin. J. Biol. Chem. 277: 23336-23344 [Abstract] [Full Text]  
• Thelen, K., Kedar, V., Panicker, A. K., Schmid, R.-S., Midkiff, B. R., Maness, P. F. (2002). The Neural Cell Adhesion Molecule L1 Potentiates Integrin-Dependent Cell Migration to Extracellular Matrix Proteins. J. Neurosci. 22: 4918-4931 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents