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PMID:15811952

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Citation

Boles, KS, Barchet, W, Diacovo, T, Cella, M and Colonna, M (2005) The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAM. Blood 106:779-86

Abstract

The tumor suppressor in lung cancer-1 (TSLC1) gene is frequently silenced in human lung carcinomas, and its expression suppresses tumorigenesis in nude mice. TSLC1 encodes a cell-surface protein called Necl-2 that belongs to the Nectin and Nectin-like (Necl) family of molecules. Necl-2 mediates epithelial cell junctions by homotypic contacts and/or heterotypic interactions with other Nectins and Necls. Thus, it inhibits tumorigenesis by ensuring that epithelial cells grow in organized layers. Here, we demonstrate that natural killer (NK) cells and CD8+ T cells recognize Necl-2 through a receptor known as class I-restricted T-cell-associated molecule (CRTAM), which is expressed only on activated cells. CRTAM-Necl-2 interactions promote cytotoxicity of NK cells and interferon gamma (IFN-gamma) secretion of CD8+ T cells in vitro as well as NK cell-mediated rejection of tumors expressing Necl-2 in vivo. These results provide evidence for an additional mechanism of tumor suppression mediated by TSLC1 that involves cytotoxic lymphocytes. Furthermore, they reveal Necl-2 as one of the molecular targets that allows the immunosurveillance network to distinguish tumor cells from normal cells.

Links

PubMed Online version:10.1182/blood-2005-02-0817

Keywords

Animals; Binding Sites; CD8-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/secretion; Cell Adhesion Molecules; Cell Line, Tumor; Cells, Cultured; Cytotoxicity, Immunologic; Humans; Immunoglobulins/genetics; Immunoglobulins/immunology; Immunoglobulins/metabolism; Interferon-gamma/secretion; Killer Cells, Natural/immunology; Lymphocyte Activation; Membrane Proteins/immunology; Membrane Proteins/metabolism; Mice; Monitoring, Immunologic; Neoplasms/immunology; Receptors, Cell Surface/immunology; Receptors, Cell Surface/metabolism; Transfection; Tumor Suppressor Proteins

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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