Mechanism of tumor cell-induced T-cell apoptosis mediated by galectin-1.
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.
Kovács-Sólyom
Ferenc
F
Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary.
Blaskó
Andrea
A
Fajka-Boja
Roberta
R
Katona
Róbert L
RL
Végh
Lea
L
Novák
Julianna
J
Szebeni
Gábor János
GJ
Krenács
László
L
Uher
Ferenc
F
Tubak
Vilmos
V
Kiss
Robert
R
Monostori
Eva
E
D017209:Apoptosis / Q000276:immunology*; D020169:Caspases / Q000378:metabolism; D002450:Cell Communication; D018920:Coculture Techniques; D018450:Disease Progression; D037483:Galectin 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019076:Transgenes / Q000235:genetics; D019139:Tumor Escape; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism
D037483:Galectin 1; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; D020169:Caspases