Impact of Helicobacter Pylori-Derived Outer Membrane Vesicles on Inflammation, Immune Responses, and Tumor Cell Migration in Breast Cancer Through the Snail/Β-Catenin Pathway.

Abstract

Background: Breast cancer remains a significant global health concern, with challenges in treating advanced stages necessitating the exploration of novel therapeutic approaches. Bacterial outer membrane vesicles (OMVs) have shown promise in cancer immunotherapy by targeting cancer cells and modulating immune responses. This study investigated the effects of Helicobacter pylori-derived OMVs on the activation of the Snail/β-Catenin gene cascade in regulating inflammation and cell migration in a mouse model of breast cancer.

Methods: The OMVs were extracted from the culture of H. pylori strain 26695 (ATCC 700392) using ultracentrifugation. In the mouse model, the vesicles were injected intraperitoneally into Balb/c mice with breast tumors. Tumor growth was assessed through histological examination of tumor samples. IgA and IgG antibodies were measured using ELISA. The expression of E-cadherin and vimentin proteins was evaluated by immunohistochemistry, and real-time PCR was used for vimentin, Snail, α-SMA, and β-catenin in serum samples from the different groups.

Results: The OMV treatment led to a significant increase in the expression of α-SMA, β-catenin, Snail, and vimentin genes, indicating a potential induction of epithelial-mesenchymal transition and enhanced cancer cell growth. Additionally, a decrease in vimentin expression and an increase in E-cadherin expression were observed, suggesting inhibition of cell migration. The study also revealed alterations in systemic IgA and IgG antibody levels, indicating potential immunomodulatory effects of OMVs.

Conclusions: These findings highlight the therapeutic potential of OMVs derived from H. pylori in breast cancer treatment by targeting gene cascades involved in cancer progression and modulating immune responses.