Please use this identifier to cite or link to this item:
https://hdl.handle.net/10216/126473
Author(s): | Severino, P Silva, M Carrascal, M Malagolini, N Chiricolo, M Venturi, G Barbaro Forleo, R Astolfi, A Catera, M Videira, P Dall'Olio, F |
Title: | Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cells expressing sialyltransferase ST3GAL1 |
Publisher: | BMC |
Issue Date: | 2018 |
Abstract: | 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 (Galß1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaa2,3Galß1,3GalNAc) 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 HT1376sT and HT1376T, 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 HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1ß, TNFa and IL-10 than that of HT1376T cells. Transcriptomic analysis revealed that ST3GAL1 overexpression and T/sT replacement modulated hundreds of genes. Several genes preserving genomic stability were down-regulated in HT1376sT cells which, as a consequence, displayed increased sensitivity to oxidative damage. After BCG challenge, the transcriptome of HT1376sT cells showed higher susceptibility to BCG modulation than that of HT1376T 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. |
URI: | https://hdl.handle.net/10216/126473 |
Source: | BMC Cancer, vol.18(1):198 |
Related Information: | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F45120%2F2008/PT info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F81860%2F2011/PT |
Document Type: | Artigo em Revista Científica Internacional |
Rights: | openAccess |
License: | https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/publicdomain/zero/1.0/ |
Appears in Collections: | I3S - Artigo em Revista Científica Internacional |
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10.1186-s12885-018-4107-1.pdf | 993.61 kB | Adobe PDF | View/Open |
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