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Immunol Lett ; 127(2): 108-18, 2010 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-19874850

RESUMO

Galectin-1 (Gal-1) has been implicated in tumor progression partly via the induction of T-cell apoptosis. However the mechanism of Gal-1 induced T-cell death was mostly studied using recombinant, soluble Gal-1 producing controversial results. To explore the true mechanism of Gal-1 and hence tumor cell-induced T-cell death, we applied co-cultures of tumor cells and T-cells thus avoiding artificial circumstances generated using recombinant protein. T-cells died when co-cultured with Gal-1-expressing but survived with Gal-1 non-expressing tumor cells. Removing tumor cell surface Gal-1 or knocking down Gal-1 expression resulted in diminution of T-cell apoptosis. Gal-1 transgenic or soluble Gal-1 treated HeLa cells became cytotoxic. Stimulation of apoptosis required interaction between the tumor and T-cells, presence of p56lck and ZAP70, decrease of mitochondrial membrane potential and caspase activation. Hence tumor cell-derived Gal-1 might efficiently contribute to tumor self-defense. Moreover this system resolves the discrepancies obtained using recombinant Gal-1 in T-cell apoptosis studies.


Assuntos
Apoptose/imunologia , Galectina 1/metabolismo , Mitocôndrias/fisiologia , Proteínas de Neoplasias/metabolismo , Neoplasias/imunologia , Linfócitos T/imunologia , Caspases/metabolismo , Comunicação Celular , Técnicas de Cocultura , Progressão da Doença , Galectina 1/genética , Galectina 1/imunologia , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Células Jurkat , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Potencial da Membrana Mitocondrial , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/fisiopatologia , RNA Interferente Pequeno/genética , Linfócitos T/patologia , Transgenes/genética , Evasão Tumoral , Proteína-Tirosina Quinase ZAP-70/genética , Proteína-Tirosina Quinase ZAP-70/metabolismo
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