Evaluation of attenuated Salmonella Typhimurium (STMΔznuABC) anticancer activity on canine mammary cancer-associated fibroblasts

IF 2.2 3区农林科学 Q1 VETERINARY SCIENCES

Research in veterinary science Pub Date : 2024-10-18 DOI:10.1016/j.rvsc.2024.105438

Barbara Chirullo , Floriana Fruscione , Genny Del Zotto , Filippo Dell'Anno , Michela Tarantino , Ilaria Porcellato , Paola Petrucci , Chiara Grazia De Ciucis , Antonello Bufalari , Lisa Guardone , Katia Cappelli , Giulia Moretti , Samanta Mecocci , Eleonora Monti , Livia De Paolis , Elisabetta Razzuoli

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引用次数: 0

Abstract

Bacteria-mediated treatments gained increasing attention as alternative therapies against tumors. An attenuated mutant strain of Salmonella enterica serovar Typhimurium (STMΔznuABC) has recently been considered as a potential new anti-cancer strategy. However, it is unclear whether this activity is tumor-induced or species-specific, and no data are available regarding STMΔznuABC on canine mammary tumors (CMTs). This study aimed to investigate the ability of STMΔznuABC in modulating the response of CMTs, focusing on cancer-associated fibroblasts. Four CMT cell lines (CF33, TM51, TM52 TM53) were treated with STMΔznuABC. Then, antiproliferative activity (MTT assay), bacterial invasion, and CMT cell lines gene expression analysis (RT-qPCR) of genes involved in immune response and cancer aggressiveness were evaluated. STMΔznuABC penetrated in TM51, TM52, TM53, and CF33 cell lines, causing a significant reduction of cell viability. Moreover, the expression of several genes was significantly modulated in all CMT cell lines: STMΔznuABC infection determined a significant up-regulation of CXCL8, IL18, IL10, TLR4 and RAD51, while CD14, IL6, CXCR4, P53, PTEN, STAT5, TLR5 and TGFB1 were downregulated in TM53. In CF33, CXCL8 and P53 were upregulated, while MYD88, MD2, IL18, TLR4,5, TGFB1 were downregulated. In TM52, CXCL8, CD44 and MD2 were upregulated and PTEN was downregulated, while in TM51 CXCL8, CD44 and ErbB2 were downregulated. We demonstrated the anti-proliferative and immuno-modulatory activity of STMΔznuABC in CMTs, paving the way for potential new anti-cancer treatments.

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评估减毒鼠伤寒沙门氏菌（STMΔznuABC）对犬乳腺癌相关成纤维细胞的抗癌活性。

细菌介导的治疗作为抗肿瘤的替代疗法越来越受到关注。最近，一种减毒突变株伤寒沙门氏菌（STMΔznuABC）被认为是一种潜在的抗癌新策略。然而，目前还不清楚这种活性是肿瘤诱导的还是物种特异性的，也没有关于STMΔznuABC对犬乳腺肿瘤（CMTs）的数据。本研究旨在研究 STMΔznuABC 调节 CMTs 反应的能力，重点是癌症相关成纤维细胞。研究人员用 STMΔznuABC 处理了四种 CMT 细胞系（CF33、TM51、TM52、TM53）。然后，评估了抗增殖活性（MTT 法）、细菌侵袭和 CMT 细胞株基因表达分析（RT-qPCR）中涉及免疫反应和癌症侵袭性的基因。STMΔznuABC可穿透TM51、TM52、TM53和CF33细胞系，显著降低细胞活力。此外，几种基因的表达在所有 CMT 细胞系中都发生了显著变化：在 TM53 中，CD14、IL6、CXCR4、P53、PTEN、STAT5、TLR5 和 TGFB1 被下调。在 CF33 中，CXCL8 和 P53 上调，而 MYD88、MD2、IL18、TLR4,5 和 TGFB1 下调。在TM52中，CXCL8、CD44和MD2上调，PTEN下调，而在TM51中，CXCL8、CD44和ErbB2下调。我们证明了 STMΔznuABC 在 CMTs 中的抗增殖和免疫调节活性，为潜在的抗癌新疗法铺平了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Research in veterinary science 农林科学-兽医学

CiteScore

4.40

自引率

4.20%

发文量

312

审稿时长

75 days

期刊介绍： Research in Veterinary Science is an International multi-disciplinary journal publishing original articles, reviews and short communications of a high scientific and ethical standard in all aspects of veterinary and biomedical research. The primary aim of the journal is to inform veterinary and biomedical scientists of significant advances in veterinary and related research through prompt publication and dissemination. Secondly, the journal aims to provide a general multi-disciplinary forum for discussion and debate of news and issues concerning veterinary science. Thirdly, to promote the dissemination of knowledge to a broader range of professions, globally. High quality papers on all species of animals are considered, particularly those considered to be of high scientific importance and originality, and with interdisciplinary interest. The journal encourages papers providing results that have clear implications for understanding disease pathogenesis and for the development of control measures or treatments, as well as those dealing with a comparative biomedical approach, which represents a substantial improvement to animal and human health. Studies without a robust scientific hypothesis or that are preliminary, or of weak originality, as well as negative results, are not appropriate for the journal. Furthermore, observational approaches, case studies or field reports lacking an advancement in general knowledge do not fall within the scope of the journal.