ALCAM/CD166: A pleiotropic mediator of cell adhesion,stemness and cancer progression |
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| Institution: | 1. Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892;2. Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan 480-1195;3. Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland 80-210;4. Department of Pathology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany 39106;5. Department of Pathology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland 01-138;6. Department of Tumor Pathology, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Krakow Branch, Poland 31-115;7. Department of Pathomorphology, Jagiellonian University, Krakow, Poland 31-007;8. Independent Laboratory of Pathology, Zdunomed, Szczecin, Poland 70-891;9. Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, MD 20892;1. Department of Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany;2. Division of Cellular and Molecular Pathology, German Cancer Research Center, INF 280, 69120 Heidelberg, Germany;3. Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68135 Mannheim, Germany;4. Department of Internal Medicine, University of Tübingen, 72074 Tübingen, Germany;5. German Center for Diabetes Research, 85764 Neuherberg, Germany;6. Department of Nephrology, University of Heidelberg, INF 410, 69120 Heidelberg, Germany;7. Institute for Diabetes and Cancer IDC, Helmholtz Center Munich and Joint Heidelberg-IDC Translational, Diabetes Program, University of Heidelberg, INF 410, 69120 Heidelberg, Germany |
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| Abstract: | Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) is a glycoprotein involved in homotypic and heterotypic cell adhesion. ALCAM can be proteolytically cleaved at the cell surface by metalloproteases, which generate shedding of its ectodomain. In various tumors, ALCAM is overexpressed and serves as a valuable prognostic marker of disease progression. Moreover, CD166 has been identified as a putative cancer stem cell marker in particular cancers. Herein, we summarize biochemical aspects of ALCAM, including structure, proteolytic shedding, alternative splicing, and specific ligands, and integrate this information with biological functions of this glycoprotein including cell adhesion, migration and invasion. In addition, we discuss different patterns of ALCAM expression in distinct tumor types and its contribution to tumor progression. Finally, we highlight the role of ALCAM as a cancer stem cell marker and introduce current clinical trials associated with this molecule. Future studies are needed to define the value of shed ALCAM in biofluids or ALCAM isoform expression as prognostic biomarkers in tumor progression. |
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| Keywords: | ALCAM/CD166 Structure Shedding Tumor progression Cancer stem cell marker |
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