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

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.