scholarly journals Helicobacter pylori and gastric cancer: a lysosomal protease perspective

2021 ◽  
Author(s):  
Surinder M. Soond ◽  
Andrey A. Zamyatnin
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Disease Progression ◽  
Molecular Mechanisms ◽  
Basic Research ◽  
Inflammatory Cells ◽  
Host Cells ◽  
Contributory Factor ◽  
Lysosomal Protease ◽  
Cathepsin Proteases

AbstractThe intimate involvement of pathogens with the heightened risk for developing certain cancers is an area of research that has captured a great deal of attention over the last 10 years. One firmly established paradigm that highlights this aspect of disease progression is in the instance of Helicobacter pylori infection and the contribution it makes in elevating the risk for developing gastric cancer. Whilst the molecular mechanisms that pinpoint the contribution that this microorganism inflicts towards host cells during gastric cancer initiation have come into greater focus, another picture that has also emerged is one that implicates the host’s immune system, and the chronic inflammation that can arise therefrom, as being a central contributory factor in disease progression. Consequently, when taken with the underlying role that the extracellular matrix plays in the development of most cancers, and how this dynamic can be modulated by proteases expressed from the tumor or inflammatory cells, a complex and detailed relationship shared between the individual cellular components and their surroundings is coming into focus. In this review article, we draw attention to the emerging role played by the cathepsin proteases in modulating the stage-specific progression of Helicobacter pylori-initiated gastric cancer and the underlying immune response, while highlighting the therapeutic significance of this dynamic and how it may be amenable for novel intervention strategies within a basic research or clinical setting.

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Induction and prevention of gastric cancer with combined Helicobacter pylori and capsaicin administration and DFMO treatment, respectively

2020 ◽  
Author(s):  
Faisal Aziz ◽  
Mingxia Xin ◽  
Yunfeng Gao ◽  
Josh Monts ◽  
Kjersten Monson ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Mouse Models ◽  
Chronic Gastritis ◽  
Molecular Mechanisms ◽  
Gastric Carcinogenesis ◽  
Lifestyle Changes ◽  
Host Susceptibility ◽  
Anti Inflammatory ◽  
H Pylori

Abstract Background: Gastric cancer risk evolves over time due to environmental, dietary, and lifestyle changes including Helicobacter pylori (H. pylori) infection and consumption of hot peppers (i.e. capsaicin). H. pylori infection promotes gastric mucosal injury in the early phase of capsaicin exposure. In addition, capsaicin consumption is reported to suppress immune function and increase host susceptibility to microbial infection. This relationship suggests a need to investigate the mechanism of how both H. pylori infection and capsaicin contribute to gastric inflammation and lead to gastric cancer. No previous experimental animal models have been developed to study this dual association. Here we developed a series of mouse models that progress from chronic gastritis to gastric cancer. C57-Balb/c mice were infected with the H. pylori (SS1) strain and then fed capsaicin (0.05% or 0.2g/kg/day) or not. Consequently, we investigated the association between H. pylori infection and capsaicin consumption during the initiation of gastric inflammation and the later development of gastric cancer. Tumor size and phenotype were analyzed to determine the molecular mechanism driving the shift from gastritis to stomach cancer. Gastric carcinogenesis was also prevented in these models using the ornithine decarboxylase inhibitor DFMO (2-difluoromethylornithine). Results: This study provides evidence showing that a combination of H. pylori infection and capsaicin consumption leads to gastric carcinogenesis. The transition from chronic gastritis to gastric cancer is mediated through interleukin-6 (IL-6) stimulation with an incidence rate of 50%. However, this progression can be prevented by treating with anti-inflammatory agents. In particular, we used DFMO to prevent gastric tumorigenesis by reducing inflammation and promoting recovery of disease-free stasis. The anti-inflammatory role of DFMO highlights the injurious effect of inflammation in gastric cancer development and the need to reduce gastric inflammation for cancer prevention. Conclusions: Overall, these mouse models provide reliable systems for analyzing the molecular mechanisms and synergistic effects of H. pylori and capsaicin on human cancer etiology. Accordingly, preventive measures like reduced capsaicin consumption, H. pylori clearance, and DFMO treatment can lessen gastric cancer incidence. Lastly, anti-inflammatory agents like DFMO can play important roles in prevention of inflammation-associated gastric cancer.

scholarly journals The Helicobacter pylori CZB Cytoplasmic Chemoreceptor TlpD Forms an Autonomous Polar Chemotaxis Signaling Complex That Mediates a Tactic Response to Oxidative Stress

2016 ◽  
Vol 198 (11) ◽  
pp. 1563-1575 ◽  
Author(s):  
Kieran D. Collins ◽  
Tessa M. Andermann ◽  
Jenny Draper ◽  
Lisa Sanders ◽  
Susan M. Williams ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Host Cells ◽  
Oxygen Species ◽  
Content Type ◽  
Signaling Complex ◽  
H Pylori

ABSTRACTCytoplasmic chemoreceptors are widespread among prokaryotes but are far less understood than transmembrane chemoreceptors, despite being implicated in many processes. One such cytoplasmic chemoreceptor isHelicobacter pyloriTlpD, which is required for stomach colonization and drives a chemotaxis response to cellular energy levels. Neither the signals sensed by TlpD nor its molecular mechanisms of action are known. We report here that TlpD functions independently of the other chemoreceptors. When TlpD is the sole chemoreceptor, it is able to localize to the pole and recruits CheW, CheA, and at least two CheV proteins to this location. It loses the normal membrane association that appears to be driven by interactions with other chemoreceptors and with CheW, CheV1, and CheA. These results suggest that TlpD can form an autonomous signaling unit. We further determined that TlpD mediates a repellent chemotaxis response to conditions that promote oxidative stress, including being in the presence of iron, hydrogen peroxide, paraquat, and metronidazole. Last, we found that all testedH. pyloristrains express TlpD, whereas other chemoreceptors were present to various degrees. Our data suggest a model in which TlpD coordinates a signaling complex that responds to oxidative stress and may allowH. pylorito avoid areas of the stomach with high concentrations of reactive oxygen species.IMPORTANCEHelicobacter pylorisenses its environment with proteins called chemoreceptors. Chemoreceptors integrate this sensory information to affect flagellum-based motility in a process called chemotaxis. Chemotaxis is employed during infection and presumably aidsH. pyloriin encountering and colonizing preferred niches. A cytoplasmic chemoreceptor named TlpD is particularly important in this process, and we report here that this chemoreceptor is able to operate independently of other chemoreceptors to organize a chemotaxis signaling complex and mediate a repellent response to oxidative stress conditions.H. pyloriencounters and must cope with oxidative stress during infection due to oxygen and reactive oxygen species produced by host cells. TlpD's repellent response may allow the bacteria to escape niches experiencing inflammation and elevated reactive oxygen species (ROS) production.

scholarly journals Molecular anatomy and pathogenic actions of Helicobacter pylori CagA that underpin gastric carcinogenesis

2019 ◽  
Vol 17 (1) ◽  
pp. 50-63 ◽  
Author(s):  
Atsushi Takahashi-Kanemitsu ◽  
Christopher T. Knight ◽  
Masanori Hatakeyama
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Tyrosine Phosphorylation ◽  
Gastric Carcinogenesis ◽  
Host Cells ◽  
Gastric Epithelial Cells ◽  
Cancer Hallmarks ◽  
Hit And Run

AbstractChronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor for gastric cancer. The cagA gene product, CagA, is delivered into gastric epithelial cells via the bacterial type IV secretion system. Delivered CagA then undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in its C-terminal region and acts as an oncogenic scaffold protein that physically interacts with multiple host signaling proteins in both tyrosine phosphorylation-dependent and -independent manners. Analysis of CagA using in vitro cultured gastric epithelial cells has indicated that the nonphysiological scaffolding actions of CagA cell-autonomously promote the malignant transformation of the cells by endowing the cells with multiple phenotypic cancer hallmarks: sustained proliferation, evasion of growth suppressors, invasiveness, resistance to cell death, and genomic instability. Transgenic expression of CagA in mice leads to in vivo oncogenic action of CagA without any overt inflammation. The in vivo oncogenic activity of CagA is further potentiated in the presence of chronic inflammation. Since Helicobacter pylori infection triggers a proinflammatory response in host cells, a feedforward stimulation loop that augments the oncogenic actions of CagA and inflammation is created in CagA-injected gastric mucosa. Given that Helicobacter pylori is no longer colonized in established gastric cancer lesions, the multistep nature of gastric cancer development should include a “hit-and-run” process of CagA action. Thus, acquisition of genetic and epigenetic alterations that compensate for CagA-directed cancer hallmarks may be required for completion of the “hit-and-run” process of gastric carcinogenesis.

Preventive Role of Resveratrol Against Inflammatory Cytokines and Related Diseases

2019 ◽  
Vol 25 (12) ◽  
pp. 1345-1371 ◽  
Author(s):  
Tanzir Rafe ◽  
Parvez Ahmed Shawon ◽  
Liyad Salem ◽  
Nafij Imtiyaj Chowdhury ◽  
Farjana Kabir ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Human Subjects ◽  
Inflammatory Cells ◽  
Host Cells ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Long Run

Background:Immunity is the ultimate barrier between foreign stimuli and a host cell. Unwanted immune responses can threaten the host cells and may eventually damage a vital organ. Overproduction of inflammatory cytokines may also lead to autoimmune diseases. Inflammatory cells and pro-inflammatory cytokines can eventually progress to renal, cardiac, brain, hepatic, pancreatic and ocular inflammation that can result in severe damage in the long run. Evidence also suggests that inflammation may lead to atherosclerosis, Alzheimer’s, hypertension, stroke, cysts and cancers.Methods:This study was designed to correlate the possible molecular mechanisms for inflammatory diseases and prevent biochemical changes owing to inflammatory cytokines by using Resveratrol. Therefore, we searched and accumulated very recent literature on inflammatory disorders and Resveratrol. We scoured PubMed, Scopus, Science Direct, PLoS One and Google Scholar to gather papers and related information.Results:Reports show that inflammatory diseases are very complex, as multiple cascade systems are involved; therefore, they are quite difficult to cure. However, our literature search also correlates some possible molecular interactions by which inflammation can be prevented. We noticed that Resveratrol is a potent lead component and has multiple activities against harmful inflammatory cytokines and related microRNA. Our study also suggests that the anti-inflammatory properties of Resveratrol have been highly studied on animal models, cell lines and human subjects and proven to be very effective in reducing inflammatory cell production and pro-inflammatory cytokine accumulation. Our tables and figures also demonstrate recent findings and possible preventive activities to minimize inflammatory diseases.Conclusion:This study would outline the role of harmful inflammatory cytokines as well as how they accelerate pathophysiology and progress to an inflammatory disorder. Therefore, this study might show a potential therapeutic value of using Resveratrol by health professionals in preventing inflammatory disorders.

scholarly journals Evodiamine Inhibits Helicobacter pylori Growth and Helicobacter pylori-Induced Inflammation

2021 ◽  
Vol 22 (7) ◽  
pp. 3385
Author(s):  
Ji Yeong Yang ◽  
Jong-Bae Kim ◽  
Pyeongjae Lee ◽  
Sa-Hyun Kim
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Secretion System ◽  
Host Cells ◽  
World Health ◽  
Ags Cells ◽  
Inhibitory Mechanisms ◽  
Anti Inflammatory ◽  
H Pylori ◽  
Bacterial Effect

Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organization (WHO) plays an important role in the progression of chronic gastritis and the development of gastric cancer. A major bioactive component of Evodia rutaecarpa, evodiamine, has been known for its anti-bacterial effect and anti-cancer effects. However, the inhibitory effect of evodiamine against H. pylori is not yet known and the inhibitory mechanisms of evodiamine against gastric cancer cells are yet to be elucidated concretely. In this study, therefore, anti-bacterial effect of evodiamine on H. pylori growth and its inhibitory mechanisms as well as anti-inflammatory effects and its mechanisms of evodiamine on H. pylori-induced inflammation were investigated in vitr. Results of this study showed the growth of the H. pylori reference strains and clinical isolates were inhibited by evodiamine. It was considered one of the inhibitory mechanisms that evodiamine downregulated both gene expressions of replication and transcription machineries of H. pylori. Treatment of evodiamine also induced downregulation of urease and diminished translocation of cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) proteins into gastric adenocarcinoma (AGS) cells. This may be resulted from the reduction of CagA and VacA expressions as well as the type IV secretion system (T4SS) components and secretion system subunit protein A (SecA) protein which are involved in translocation of CagA and VacA into host cells, respectively. In particular, evodiamine inhibited the activation of signaling proteins such as the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway induced by H. pylori infection. It consequently might contribute to reduction of interleukin (IL)-8 production in AGS cells. Collectively, these results suggest anti-bacterial and anti-inflammatory effects of evodiamine against H. pylori.

scholarly journals Engagement of CEACAM1 by Helicobacter pylori HopQ Is Important for the Activation of Non-Canonical NF-κB in Gastric Epithelial Cells

2021 ◽  
Vol 9 (8) ◽  
pp. 1748
Author(s):  
Karin Taxauer ◽  
Youssef Hamway ◽  
Anna Ralser ◽  
Alisa Dietl ◽  
Karin Mink ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Surface Protein ◽  
Host Cells ◽  
Gastric Epithelial Cells ◽  
Gastric Cancer Cells ◽  
Tissue Samples ◽  
Mutant Strains ◽  
H Pylori

The gastric pathogen Helicobacter pylori infects half of the world’s population and is a major risk factor for gastric cancer development. In order to attach to human gastric epithelial cells and inject the oncoprotein CagA into host cells, H. pylori utilizes the outer membrane protein HopQ that binds to the cell surface protein CEACAM, which can be expressed on the gastric mucosa. Once bound, H. pylori activates a number of signaling pathways, including canonical and non-canonical NF-κB. We investigated whether HopQ–CEACAM interaction is involved in activating the non-canonical NF-κB signaling pathway. Different gastric cancer cells were infected with the H. pylori wild type, or HopQ mutant strains, and the activation of non-canonical NF-κB was related to CEACAM expression levels. The correlation between CEACAM levels and the activation of non-canonical NF-κB was confirmed in human gastric tissue samples. Taken together, our findings show that the HopQ–CEACAM interaction is important for activation of the non-canonical NF-κB pathway in gastric epithelial cells.

scholarly journals Lactobacilli Reduce Helicobacter pylori Attachment to Host Gastric Epithelial Cells by Inhibiting Adhesion Gene Expression

2016 ◽  
Vol 84 (5) ◽  
pp. 1526-1535 ◽  
Author(s):  
Nele de Klerk ◽  
Lisa Maudsdotter ◽  
Hanna Gebreegziabher ◽  
Sunil D. Saroj ◽  
Beatrice Eriksson ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Binding Capacity ◽  
Host Cells ◽  
Gastric Epithelial Cells ◽  
Content Type ◽  
Effector Molecule ◽  
H Pylori

The human gastrointestinal tract, including the harsh environment of the stomach, harbors a large variety of bacteria, of whichLactobacillusspecies are prominent members. The molecular mechanisms by which species of lactobacilli interfere with pathogen colonization are not fully characterized. In this study, we aimed to study the effect of lactobacillus strains upon the initial attachment ofHelicobacter pylorito host cells. Here we report a novel mechanism by which lactobacilli inhibit adherence of the gastric pathogenH. pylori. In a screen withLactobacillusisolates, we found that only a few could reduce adherence ofH. pylorito gastric epithelial cells. Decreased attachment was not due to competition for space or to lactobacillus-mediated killing of the pathogen. Instead, we show that lactobacilli act onH. pyloridirectly by an effector molecule that is released into the medium. This effector molecule acts onH. pyloriby inhibiting expression of the adhesin-encoding genesabA. Finally, we verified that inhibitory lactobacilli reducedH. pyloricolonization in anin vivomodel. In conclusion, certainLactobacillusstrains affect pathogen adherence by inhibitingsabAexpression and thereby reducingH. pyloribinding capacity.

scholarly journals In Vivo Analysis of the Viable Microbiota and Helicobacter pylori Transcriptome in Gastric Infection and Early Stages of Carcinogenesis

2017 ◽  
Vol 85 (10) ◽  
Author(s):  
Kaisa Thorell ◽  
Johan Bengtsson-Palme ◽  
Oscar Hsin-Fu Liu ◽  
Reyna Victoria Palacios Gonzales ◽  
Intawat Nookaew ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Disease Progression ◽  
Ph Regulation ◽  
Gastric Ulcers ◽  
Gastric Disease ◽  
Content Type ◽  
Expression Of Genes ◽  
H Pylori

ABSTRACT Emerging evidence shows that the human microbiota plays a larger role in disease progression and health than previously anticipated. Helicobacter pylori, the causative agent of gastric cancer and duodenal and gastric ulcers, was early associated with gastric disease, but it has also been proposed that the accompanying microbiota in Helicobacter pylori-infected individuals might affect disease progression and gastric cancer development. In this study, the composition of the transcriptionally active microbial community and H. pylori gene expression were determined using metatranscriptomic RNA sequencing of stomach biopsy specimens from individuals with different H. pylori infection statuses and premalignant tissue changes. The results show that H. pylori completely dominates the microbiota not only in infected individuals but also in most individuals classified as H. pylori uninfected using conventional methods. Furthermore, H. pylori abundance is positively correlated with the presence of Campylobacter, Deinococcus, and Sulfurospirillum. Finally, we quantified the expression of a large number of Helicobacter pylori genes and found high expression of genes involved in pH regulation and nickel transport. Our study is the first to dissect the viable microbiota of the human stomach by metatranscriptomic analysis, and it shows that metatranscriptomic analysis of the gastric microbiota is feasible and can provide new insights into how bacteria respond in vivo to variations in the stomach microenvironment and at different stages of disease progression.

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