Lipopolysaccharide exacerbates to the migration, invasion, and epithelial‐mesenchymal transition of esophageal cancer cells by TLR4/NF‐κB axis

Previous studies have shown the role of bacterial lipopolysaccharide (LPS) in promoting tumor progression. Our previous study found that the community richness of LPS‐producing bacteria was significantly increased in the fresh stool samples of esophageal cancer (EC) patients, but the relative LPS levels and underlying mechanism in EC progression remain unknown. In this study, an case‐control study found that the content of LPS was higher in serum of EC patients. Functional experiments of CCK8 assay and transwell assay showed that LPS contributed to the proliferation, migration, invasion of EC109 cells. Meanwhile, LPS induced EC109 to secrete IL‐6 and TGF‐β1. Western blot analysis revealed the level of TLR4 and NF‐κB increased significantly after LPS treatment. Epithelial marker E‐cadherin was significantly down‐regulated and interstitial marker N‐cadherin and Vimentin were up‐regulated after LPS treatment. However, TAK242 (TLR4 inhibitor) or PDTC (NF‐κB inhibitor) could eliminate the inflammatory and EMT—promoting effects of LPS. In total, our results suggested that LPS exacerbated to the migration, invasion, and epithelial‐mesenchymal transition of EC109 cells by TLR4/NF‐κB axis. High level LPS may have a critical effect on the occurrence and development of EC.

[1]  N. Sekido,et al.  The first case of Veillonella atypica bacteremia in a patient with renal pelvic tumor. , 2021, Anaerobe.

[2]  Wenchuan Wu,et al.  Gut-derived lipopolysaccharide remodels tumoral microenvironment and synergizes with PD-L1 checkpoint blockade via TLR4/MyD88/AKT/NF-κB pathway in pancreatic cancer , 2021, Cell Death & Disease.

[3]  Z. Soons,et al.  Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients , 2021, Journal of cachexia, sarcopenia and muscle.

[4]  Shukui Wang,et al.  Characterization of Esophageal Microbiota in Patients With Esophagitis and Esophageal Squamous Cell Carcinoma , 2021, Frontiers in Cellular and Infection Microbiology.

[5]  E. Tagliabue,et al.  Toll Like Receptors as Sensors of the Tumor Microbial Dysbiosis: Implications in Cancer Progression , 2021, Frontiers in Cell and Developmental Biology.

[6]  N. Zhang,et al.  Pediococcus pentosaceus PP04 improves high-fat diet-induced liver injury by the modulation of gut inflammation and intestinal microbiota in C57BL/6N mice. , 2021, Food & function.

[7]  Hong Xu,et al.  Mucosal microbial microenvironment in early gastric neoplasia and non‐neoplastic gastric disease , 2021, Journal of gastroenterology and hepatology.

[8]  F. Cardinale,et al.  Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo , 2021, Microorganisms.

[9]  R. Sankar,et al.  Disruption of intestinal barrier and endotoxemia after traumatic brain injury: Implications for post‐traumatic epilepsy , 2021, Epilepsia.

[10]  J. Ferlay,et al.  Cancer statistics for the year 2020: An overview , 2021, International journal of cancer.

[11]  Tao Wu,et al.  Role and clinical significance of TGF-β1 and TGF-βR1 in malignant tumors (Review) , 2021, International journal of molecular medicine.

[12]  Gwangbeom Heo,et al.  Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer , 2021, Cancers.

[13]  Y. Lai,et al.  Two ST11 Klebsiella pneumoniae strains exacerbate colorectal tumorigenesis in a colitis-associated mouse model , 2021, Gut microbes.

[14]  Baolin Sun,et al.  Gastrointestinal Microbiota Changes in Patients With Gastric Precancerous Lesions , 2020, Frontiers in Cellular and Infection Microbiology.

[15]  Tian Wang,et al.  Dysbiosis of gut microbiota in patients with esophageal cancer. , 2020, Microbial pathogenesis.

[16]  F. Cobo,et al.  Bacteremia caused by Veillonella dispar in an oncological patient , 2020, Anaerobe.

[17]  A. Green,et al.  IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis. , 2020, Cancer cell.

[18]  Edward L. Giovannucci,et al.  Global Burden of 5 Major Types Of Gastrointestinal Cancer. , 2020, Gastroenterology.

[19]  F. Bazzoli,et al.  Gastric cancer prevention strategies: A global perspective , 2020, Journal of gastroenterology and hepatology.

[20]  R. S. Saia,et al.  Cholecystokinin Modulates the Mucosal Inflammatory Response and Prevents the Lipopolysaccharide-Induced Intestinal Epithelial Barrier Dysfunction. , 2020, Shock.

[21]  G. Carpino,et al.  Increased Liver Localization of Lipopolysaccharides in Human and Experimental NAFLD , 2019, Hepatology.

[22]  R. Hoffman,et al.  MyD88 Regulates LPS-induced NF-ĸB/MAPK Cytokines and Promotes Inflammation and Malignancy in Colorectal Cancer Cells , 2019, Cancer Genomics & Proteomics.

[23]  H. Suganuma,et al.  Regulation of Gut Microbiota and Metabolic Endotoxemia with Dietary Factors , 2019, Nutrients.

[24]  Guy C. Brown The endotoxin hypothesis of neurodegeneration , 2019, Journal of Neuroinflammation.

[25]  Heping Zhao,et al.  Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma , 2019, World journal of gastroenterology.

[26]  C. Blanpain,et al.  EMT Transition States during Tumor Progression and Metastasis. , 2019, Trends in cell biology.

[27]  Huanbai Xu,et al.  LPS-induced CXCR7 expression promotes gastric Cancer proliferation and migration via the TLR4/MD-2 pathway , 2019, Diagnostic Pathology.

[28]  Jie He,et al.  Cancer incidence and mortality in China, 2014. , 2018, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[29]  C. Abnet,et al.  Epidemiology of Esophageal Squamous Cell Carcinoma. , 2017, Gastroenterology.

[30]  Yongdong Feng,et al.  Human colorectal cancer-derived mesenchymal stem cells promote colorectal cancer progression through IL-6/JAK2/STAT3 signaling , 2018, Cell Death & Disease.

[31]  M. Zhou,et al.  Trend analysis of cancer incidence and mortality in China , 2017, Science China Life Sciences.

[32]  He Wang,et al.  Baicalin Alleviates Lipopolysaccharide-Induced Liver Inflammation in Chicken by Suppressing TLR4-Mediated NF-κB Pathway , 2017, Front. Pharmacol..

[33]  C. Gilles,et al.  EMT and inflammation: inseparable actors of cancer progression , 2017, Molecular oncology.

[34]  Masayuki Watanabe,et al.  Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications , 2017, Annals of gastroenterological surgery.

[35]  Simion I. Chiosea,et al.  Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations , 2017, Nature Communications.

[36]  T. Deng,et al.  Lipopolysaccharide-induced toll-like receptor 4 signaling in esophageal squamous cell carcinoma promotes tumor proliferation and regulates inflammatory cytokines expression. , 2016, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[37]  A. Rashid,et al.  Lipopolysaccharide-pathway proteins are associated with gallbladder cancer among adults in Shanghai, China with mediation by systemic inflammation. , 2016, Annals of epidemiology.

[38]  P. Bechi,et al.  The esophageal microbiota in health and disease , 2016, Annals of the New York Academy of Sciences.

[39]  Aizhong Wang,et al.  Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling. , 2016, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[40]  Sangdun Choi,et al.  Toll-like receptors: promising therapeutic targets for inflammatory diseases , 2016, Archives of Pharmacal Research.

[41]  Xiyu Liu,et al.  TLR4/ROS/miRNA-21 pathway underlies lipopolysaccharide instructed primary tumor outgrowth in lung cancer patients , 2016, Oncotarget.

[42]  M. Braddock,et al.  Toll-like receptors in hepatocellular carcinoma: potential novel targets for pharmacological intervention , 2016, Expert opinion on therapeutic targets.

[43]  Z. Pei,et al.  Microbiome in reflux disorders and esophageal adenocarcinoma. , 2014, Cancer journal.

[44]  Mingyong Han,et al.  Systemic inflammation promotes lung metastasis via E-selectin upregulation in mouse breast cancer model , 2014, Cancer biology & therapy.

[45]  A. Alayash,et al.  Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. , 2014, Blood.

[46]  Y. Zeng,et al.  Tumor Microenvironment Macrophage Inhibitory Factor Directs the Accumulation of Interleukin-17-producing Tumor-infiltrating Lymphocytes and Predicts Favorable Survival in Nasopharyngeal Carcinoma Patients* , 2012, The Journal of Biological Chemistry.

[47]  Liping Zhao,et al.  Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers , 2011, The ISME Journal.

[48]  Jürgen Hoffmann,et al.  Interleukin‐6 promotes tumorigenesis by altering DNA methylation in oral cancer cells , 2011, International journal of cancer.

[49]  C. Croce,et al.  Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer , 2011, Proceedings of the National Academy of Sciences.

[50]  J. L. Pozo Primers on molecular pathways: lipopolysaccharide signaling - potential role in pancreatitis and pancreatic cancer. , 2010 .

[51]  Masafumi Nakamura,et al.  Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells through the TLR4/MyD88 signaling pathway , 2009, Journal of surgical oncology.

[52]  M. Pirisi,et al.  Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival , 2006, Cancer Immunology, Immunotherapy.

[53]  S. Akira,et al.  Toll-like receptors: critical proteins linking innate and acquired immunity , 2001, Nature Immunology.

[54]  F W MULSOW,et al.  Cancer incidence and mortality , 2019, Health at a Glance: Europe.