Lipopolysaccharide from the commensal microbiota of the breast enhances cancer growth: role of S100A7 and TLR4

Wilkie, Tasha; Verma, Ajeet Kumar; Zhao, Helong; Charan, Manish; Ahirwar, Dinesh K.; Kant, Sashi; Pancholi, Vijay; Mishra, Sanjay; Ganju, Ramesh K.

doi:10.1002/1878-0261.12975

Cited by 12 publications

(11 citation statements)

References 77 publications

(122 reference statements)

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“…LPS, which is a cell wall component of Gram-negative bacteria, was widely used to induce mastitis model in vivo and in vitro ( 42 – 45 ). It is reported that LPS from the commensal microbiota of the human breast induced the expression of S100A7 in breast cancer cells ( 46 ). Consistent with previous reports, after treatment with LPS, the inflammatory response-related factors, including IL-6, IL-1β, and TNF-α, were obviously increased.…”

Section: Discussionmentioning

confidence: 99%

C-Type Natriuretic Peptide Regulates the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway

et al. 2022

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During infection, the infected tissue secretes a variety of endogenous peptides to resist further invasion of pathogens. Among these endogenous peptides, the natriuretic peptides and the antimicrobial peptides attracted the most attention. C-type natriuretic peptide (CNP) and its receptor natriuretic peptide receptor B (NPR-B) were members of the natriuretic peptide system. The antimicrobial peptide S100A7 plays an important role to resist infection of bacteria in mastitis. It is reported that the expression of S100A7 is regulated by an activator protein-1 (AP-1)-responsive promoter. As a subunit of AP-1, c-Jun is a downstream target of CNP/NPR-B signaling pathway. Therefore, it is a hypothesis that the CNP/NPR-B signaling pathway induces the expression and secretion of S100A7 in mammary glands to take part in local mammary gland innate immunity. To verify this hypothesis, goat mammary gland and isolated mammary epithelial cells (MECs) were used to explore the expression of CNP/NPR-B and their physiological roles in goat mammary gland. The results showed that goat mammary gland expressed NPR-B, but not CNP. The expression and secretion of S100A7 in goat MECs were obviously induced by CNP/NPR-B signaling pathway. After treatment with CNP, the cyclic guanosine monophosphate (cGMP) level in goat MECs was significantly upregulated. Along with the upregulation of cGMP level, the phosphorylation levels of c-Jun N-terminal kinase (JNK) and its target c-Jun were also increased gradually. KT5823 is a specific inhibitor for protein kinase G (PKG). KT5823 remarkably inhibited the phosphorylation of JNK and c-Jun induced by CNP. Correspondingly, KT5823 evidently inhibited the expression and secretion of S100A7 induced by CNP. On the other hand, the expression of NPR-B and S100A7 was upregulated in the mastitis goat mammary gland. But, there was no significant difference in expression of CNP between healthy and mastitis goat mammary gland tissues. The goat mastitis model was established in vitro using goat MECs treated by lipopolysaccharide (LPS). LPS treatment also could increase the expression of NPR-B and S100A7. In conclusion, goat mammary gland expressed NPR-B, indicating mammary gland was the target organ for natriuretic peptide system. Moreover, CNP, through NPR-B/JNK/c-Jun signaling pathway to regulate the expression and secretion of S100A7 in MECs, played an important role in mammary gland innate immunity.

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Section: Discussionmentioning

confidence: 99%

C-Type Natriuretic Peptide Regulates the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway

et al. 2022

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“…Moreover, a previous study demonstrated that the breast tumor microbiota was enriched with Gram-negative bacteria producing LPS. In vitro LPS treatment was shown to upregulate S100A7 expression in breast cancer cells, resulting in the upregulation of RAGE expression along with a reduced TLR4 expression that may contribute to tumor growth progression (115).…”

Section: Role Of Lipopolysaccharide In the Interplay Between Microbio...mentioning

confidence: 99%

Role of gut microbiota in the modulation of the health effects of advanced glycation end‑products (Review)

et al. 2023

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The aim of the present review was to summarize the potential interactive effects between the gut microbiota and advanced glycation end-product (AGE) accumulation and toxicity in the host, and to reveal potential the mediatory effects of the gut microbiota on AGE-related health effects. The existing data demonstrate that dietary AGEs can have a significant impact on the richness and diversity of the gut microbiota, although the particular effect is dependent on the type of species, as well as the exposure dose. In addition, the gut microbiota may metabolize dietary AGEs. It has been also demonstrated that the characteristics of the gut microbiota, including its richness and relative abundance of certain taxa, is tightly associated with AGE accumulation in the host organism. In turn, a bilateral interplay between AGE toxicity and the modulation of the gut microbiota may contribute to pathogenesis of ageing and diabetes-associated diseases. Bacterial endotoxin lipopolysaccharide appears as the molecule that mediates the interactions between the gut microbiota and AGE toxicity, specifically via the modulation of the receptor for AGE signaling. Therefore, it is proposed that the modulation of the gut microbiota using probiotics or other dietary interventions may have a significant impact on AGE-induced glycative stress and systemic inflammation. Contents1. Introduction 2. Bacterial AGE metabolism 3. The impact of dietary AGE exposure on gut microbiota characteristics and host metabolism 4. Involvement of AGE-gut microbiota interplay in disease pathogenesis 5. Effects of gut microbiota modulation on AGE metabolism and toxicity 6. Role of lipopolysaccharide in the interplay between microbiota and AGE toxicity 7. Conclusions and future perspectives

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“…Notably, among multiple cancers, a particularly rich and diverse microbiome has been observed in BC [ 33 ]. Wilkie et al revealed that BC commensal microbiota is distinctly composed of Gram-negative bacteria and highlighted the role of bacterial components in BC development [ 34 ]. As one of the recently identified BC-related microbes, F. nucleatum has gained the most attention.…”

Section: Discussionmentioning

confidence: 99%

Fusobacterium nucleatum-derived small extracellular vesicles facilitate tumor growth and metastasis via TLR4 in breast cancer

Sun

Huang

et al. 2023

BMC Cancer

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Background The contributive role of the microbiome in tumor progression has been reported in multiple studies, such as the Fusobacterium nucleatum (F. nucleatum) in breast cancer (BC). This study aimed to explore the role of F. nucleatum-derived small extracellular vesicles (Fn-EVs) in BC and preliminarily uncover the mechanism. Methods Ten normal and 20 cancerous breast tissues were harvested to investigate the gDNA expression of F. nucleatum and its relation with the clinical characteristics of BC patients. After isolating Fn-EVs by ultracentrifugation from F. nucleatum (ATCC 25,586), both MDA-MB-231 and MCF-7 cells were treated with PBS, Fn, or Fn-EVs, followed by being subjected to CCK-8, Edu staining, wound healing, and Transwell assays to detect their cell viability, proliferation, migration, and invasion. TLR4 expression in BC cells with diverse treatments was assessed by western blot. In vivo experiments were performed to verify its role in tumor growth and liver metastasis. Results The F. nucleatum gDNA levels of breast tissues in BC patients were significantly higher than those in normal subjects, and positively associated with tumor size and metastasis. Fn-EVs administration significantly enhanced the cell viability, proliferation, migration, and invasion of BC cells, while knocking down TLR4 in BC cells could block these effects. Furthermore, in vivo study verified the contributive role of Fn-EVs in tumor growth and metastasis of BC, which might rely on its regulation of TLR4. Conclusions Collectively, our results suggest that F. nucleatum plays an important role in BC tumor growth and metastasis by regulating TLR4 through Fn-EVs. Thus, a better understanding of this process may aid in the development of novel therapeutic agents.

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Lipopolysaccharide from the commensal microbiota of the breast enhances cancer growth: role of S100A7 and TLR4

Cited by 12 publications

References 77 publications

C-Type Natriuretic Peptide Regulates the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway

C-Type Natriuretic Peptide Regulates the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway

Role of gut microbiota in the modulation of the health effects of advanced glycation end‑products (Review)

Fusobacterium nucleatum-derived small extracellular vesicles facilitate tumor growth and metastasis via TLR4 in breast cancer

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