Mechanism of tumor cell-induced T-cell apoptosis mediated by galectin-1

Kovács-Sólyom, Ferenc; Blaskó, Andrea; Fajka‐Boja, Roberta; Katona, Róbert L.; Végh, Lea; Novák, Julianna; Szebeni, Gábor J.; Krenács, László; Uher, Ferenc; Tubák, Vilmos; Kiss, Róbert; Monostori, Éva

doi:10.1016/j.imlet.2009.10.003

Cited by 89 publications

(125 citation statements)

References 44 publications

(79 reference statements)

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“…HeLa human cervix adenocarcinoma cells were transfected as described previously [4]. Mock transfected (HeLa mock ) or Gal-1 transgenic (HeLa Gal ) human cervix adenocarcinoma cells were cultured in MEM (Gibco) supplemented with 100 IU penicillin, 100 µg/ml streptomycin, 2mM L-glutamine and 10% FCS.…”

Section: Cellsmentioning

confidence: 99%

“…Gal-1, presented on the cell surface, was detected using a mouse anti-human Gal-1 monoclonal antibody (clone 2c1/6, produced in our laboratory [4]). For detection of inGal-1, the cells were permeabilized in IFB containing 0.1% Triton-X 100 prior to adding the anti-Gal-1 antibody.…”

Section: Indirect Immunofluorescence and Cytofluorimetrymentioning

confidence: 99%

“…T-cell apoptosis induced in co-culture: the apoptosis induced by cell-derived Gal-1 was detected as previously described [4]. Briefly, HeLa mock (control) or HeLa Gal cells The following primer sequences were used:…”

Section: Apoptosis Assays T-cell Apoptosis Induced By Soluble Gal-1: mentioning

confidence: 99%

“…It has well-defined roles in maintaining immunohomeostasis [1,2] partly via the induction of apoptosis of activated T-cells, a function that has been attributed to its secreted form [3]. The mechanism of Gal-1-triggered cell death has extensively been studied in vitro and presented by our group and others [4,5]. As it has been shown, stimulation of apoptosis requires the presence of p56lck and ZAP70 kinases, release of ceramide, decrease of mitochondrial membrane potential and caspase activation [4,6,7] and requires the direct interaction between T-cells and the surrounding environment (cells or extracellular matrix) [4].…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism of Gal-1-triggered cell death has extensively been studied in vitro and presented by our group and others [4,5]. As it has been shown, stimulation of apoptosis requires the presence of p56lck and ZAP70 kinases, release of ceramide, decrease of mitochondrial membrane potential and caspase activation [4,6,7] and requires the direct interaction between T-cells and the surrounding environment (cells or extracellular matrix) [4]. Immunoregulatory function of Gal-1 has also been confirmed by in vivo experiments [5].…”

Section: Introductionmentioning

confidence: 99%

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Novel role for galectin-1 in T-cells under physiological and pathological conditions

Deák¹,

Hornung²,

Novák³

et al. 2015

Immunobiology

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Secreted, extracellular galectin-1 (exGal-1) but not intracellular Gal-1 (inGal-1) has been described as a strong immunosuppressive protein due to its major activity of inducing apoptosis of activated T-cells. It has previously been reported that T-cells express Gal-1 upon activation, however its participation in T-cell functions has remained largely elusive. To determine function of Gal-1 expressed by activated Tcells we have carried out a series of experiments. We have shown that Gal-1, expressed in Gal-1-transgenic Jurkat cells or in activated T-cells, remained intracellularly indicating that Gal-1-induced T-cell death was not a result of an autocrine effect of the de novo expressed Gal-1. Rather, a particular consequence of the inGal-1 expression was that T-cells became more sensitive to exGal-1 added either as a soluble protein or bound to the surface of a Gal-1-secreting effector cell. This was also verified when the susceptibility of activated T-cells from wild type or Gal-1 knockout mice to Gal-1-induced apoptosis were compared. Murine T-cells expressing Gal-1 were more sensitive to the cytotoxicity of the exGal-1 than their Gal-1 knockout counterparts. We also conducted a study with activated T-cells from patients with systemic lupus erythematosus (SLE), a disease in which dysregulated T-cell apoptosis has been well described. SLE T-cells expressed lower amounts of Gal-1 than healthy T-cells and were less sensitive to exGal-1. These results suggested a novel role of inGal-1 in T-cells as a regulator of T-cell response to exGal-1, and its likely contribution to the mechanism in T-cell apoptosis deficiency in lupus.

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Section: Cellsmentioning

confidence: 99%

Section: Indirect Immunofluorescence and Cytofluorimetrymentioning

confidence: 99%

Section: Apoptosis Assays T-cell Apoptosis Induced By Soluble Gal-1: mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Novel role for galectin-1 in T-cells under physiological and pathological conditions

Deák¹,

Hornung²,

Novák³

et al. 2015

Immunobiology

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Conjugating 4β‐NH‐(5‐Aminoindazole)‐podophyllotoxin and Galectin‐1‐Targeted Aptamer for Synergistic Chemo‐Immunotherapy of Hepatocellular Carcinoma

Cong

Zhang

Tang³

et al. 2023

Adv Healthcare Materials

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By conjugating a chemotherapeutic candidate drug 4β‐NH‐(5‐aminoindazole)‐podophyllotoxin (βIZP) and an immunosuppressive protein galectin‐1 targeted aptamer AP74, a chemo‐immunotherapy molecule (AP74‐βIZP) is developed against liver cancer. AP74‐βIZP can target galectin‐1 and enrich the tumor microenvironment to improve the tumor inhibition ratio by 6.3%, higher than that of βIZP in a HepG2 xenograft model. In safety evaluation, βIZP cannot be released from AP74‐βIZP in normal tissues with low glutathione level. Therefore, the degrees of organs injury and myelosuppression after the treatment with AP74‐βIZP are lower than those with βIZP. After 21 d treatment at a drug dose of 5 mg kg−1, AP74‐βIZP does not cause weight loss in mice, while the weight is significantly reduced by 24% and 14% from oxaliplatin and βIZP, respectively. In immune synergy, AP74‐IZP enhances CD4/CD8 cell infiltration to promote the expression of cell factor (i.e., IL‐2, TNF‐α, and IFN‐γ), which further improves the antitumor activity. The tumor inhibition ratio of AP74‐βIZP is 70.2%, which is higher than that of AP74 (35.2%) and βIZP (48.8%). Because of the dual effects of chemotherapy and immunotherapy, AP74‐βIZP exhibits superior activity and lower toxicity. The approach developed in this work could be applicable to other chemotherapy drugs.

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‘Omics driven discoveries of gene targets for apoptosis attenuation in CHO cells

Orellana

Martínez

MacDonald

et al. 2020

Biotech & Bioengineering

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Chinese hamster ovary (CHO) cells are widely used in biopharmaceutical production. Improvements to cell lines and bioprocesses are constantly being explored. One of the major limitations of CHO cell culture is that the cells undergo apoptosis, leading to rapid cell death, which impedes reaching high recombinant protein titres. While several genetic engineering strategies have been successfully employed to reduce apoptosis, there is still room to further enhance CHO cell lines performance. 'Omics analysis is a powerful tool to better understand different phenotypes and for the identification of gene targets for engineering. Here, we present a comprehensive review of previous CHO 'omics studies that revealed changes in the expression of apoptosis-related genes. We highlight targets for genetic engineering that have reduced, or have the potential to reduce, apoptosis or to increase cell proliferation in CHO cells, with the final aim of increasing productivity.

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Mechanism of tumor cell-induced T-cell apoptosis mediated by galectin-1

Cited by 89 publications

References 44 publications

Novel role for galectin-1 in T-cells under physiological and pathological conditions

Novel role for galectin-1 in T-cells under physiological and pathological conditions

Conjugating 4β‐NH‐(5‐Aminoindazole)‐podophyllotoxin and Galectin‐1‐Targeted Aptamer for Synergistic Chemo‐Immunotherapy of Hepatocellular Carcinoma

‘Omics driven discoveries of gene targets for apoptosis attenuation in CHO cells

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