Lipopolysaccharide from the commensal microbiota of the breast enhances cancer growth: role of S100A7 and TLR4. Issue 7 (16th November 2021)

• Record Type: Journal Article
• Authors: Wilkie, Tasha; Verma, Ajeet K.; Zhao, Helong; Charan, Manish; Ahirwar, Dinesh K.; Kant, Sashi; Pancholi, Vijay; Mishra, Sanjay; Ganju, Ramesh K.
• Is Part Of: Molecular oncology. Volume 16:Issue 7(2022)
• Page Start: 1508
• Page End: 1522
• Publication Date: 2021-11-16
• Subjects: breast cancer -- LPS -- microbiota -- RAGE -- S100A7 -- TLR4; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12975
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : The role of commensal bacterial microbiota in the pathogenesis of human malignancies has been a research field of incomparable progress in recent years. Although breast tissue is commonly assumed to be sterile, recent studies suggest that human breast tissue may contain a bacterial microbiota. In this study, we used an immune‐competent orthotopic breast cancer mouse model to explore the existence of a unique and independent bacterial microbiota in breast tumors. We observed some similarities in breast cancer microbiota with skin; however, breast tumor microbiota was mainly enriched with Gram‐negative bacteria, serving as a primary source of lipopolysaccharide (LPS). In addition, dextran sulfate sodium (DSS) treatment in late‐stage tumor lesions increased LPS levels in the breast tissue environment. We also discovered an increased expression of S100A7 and low level of TLR4 in late‐stage tumors with or without DSS as compared to early‐stage tumor lesions. The treatment of breast cancer cells with LPS increased the expression of S100A7 in breast cancer cells in vitro . Furthermore, S100A7 overexpression downregulated TLR4 and upregulated RAGE expression in breast cancer cells. Analysis of human breast cancer samples also highlighted the inverse correlation between S100A7 and TLR4 expression. Overall, these findings suggest that the commensal microbiota of breast tissue may enhance breast tumor burden through a novel LPS/S100A7/TLR4/RAGE signaling axis. Abstract : The role of commensal microbiota in breast tumorigenesis has been a research field of incomparable progress in last few years. In this study, Wilkie et al . discuss the functional role of breast tumor microbiota‐derived lipopolysaccharide, which enhances cancer growth through differentially regulating the S100A7/TLR4 expression. This study highlights the role of microbiota and associated signaling in the breast tumor microenvironment.