Dataset Information

Oxidative damage and response to Bacillus Calmette-Guerin in bladder cancer cells expressing sialyltransferase ST3GAL1.

ABSTRACT:

Background

Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients. NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Gal?1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Sia?2,3Gal?1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.

Methods

The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376_sT and HT1376_T, that express, respectively, either the sT or the T antigens. Cells were in vitro challenged with BCG. Whole gene expression was studied by microarray technology, cytokine secretion was measured by multiplex immune-beads assay. Human macrophages derived from blood monocytes were challenged with the secretome of BCG-challenged BC cells.

Results

The secretome from BCG-challenged HT1376_sT cells induced a stronger macrophage secretion of IL-6, IL-1?, TNF? and IL-10 than that of HT1376_T cells. Transcriptomic analysis revealed that ST3GAL1 overexpression and T/sT replacement modulated hundreds of genes. Several genes preserving genomic stability were down-regulated in HT1376_sT cells which, as a consequence, displayed increased sensitivity to oxidative damage. After BCG challenge, the transcriptome of HT1376_sT cells showed higher susceptibility to BCG modulation than that of HT1376_T cells.

Conclusions

High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.

SUBMITTER: Severino PF

PROVIDER: S-EPMC5816560 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cells expressing sialyltransferase ST3GAL1.

Severino Paulo F PF Silva Mariana M Carrascal Mylene M Malagolini Nadia N Chiricolo Mariella M Venturi Giulia G Barbaro Forleo Roberto R Astolfi Annalisa A Catera Mariangela M Videira Paula A PA Dall'Olio Fabio F

BMC cancer 20180217 1

<h4>Background</h4>Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients. NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.<h4>Methods</h4>T ...[more]

PMID: 29454317

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