Stem Cells, Helicobacter pylori, and Mutational Landscape: Utility of Preclinical Models to Understand Carcinogenesis and to Direct Management of Gastric Cancer

Liabeuf, Dylan; Oshima, Masanobu; Stange, Daniel E.; Sigal, Michael

doi:10.1053/j.gastro.2021.12.252

Cited by 28 publications

(11 citation statements)

References 160 publications

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“…Zu diesen Botenstoffen gehört auch das „Bone Morphogenetic Protein“ (BMP), das für die Gewebeentwicklung von Bedeutung ist. Die Forschen konnten zeigen, dass Stromazellen, die die Drüsenbasis umgeben, den BMP-Signalweg fortwährend unterdrücken und so die Teilung der dortigen Stammzellen anregen 1 , 2 . Hingegen aktivieren Stromazellen an der Drüsenspitze den Signalweg und unterbinden damit dort die Zellteilung.…”

Section: Signalübertragung Von Magenzellen Gestörtunclassified

Helicobacter pylori und Magenkarzinom

2022

Onkologische Welt

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Eine Infektion der Magenschleimhaut mit dem Helicobacter-Bakterium führt zu Magenentzündungen und erhöht das Risiko für Magenkrebs. Ein Forschungsteam hat jetzt einen bisher unbekannten Mechanismus gefunden, der die Zellteilung im gesunden Gewebe begrenzt und somit vor Krebsentwicklung schützt. Durch eine Mageninfektion wird dieser aufgehoben, so dass die Zellen unkontrolliert wachsen können.

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Section: Signalübertragung Von Magenzellen Gestörtunclassified

Helicobacter pylori und Magenkarzinom

2022

Onkologische Welt

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“…In addition, a subpopulation of H. pylori can form colonies deep inside the gastric glands, where stem and progenitor cells reside (Sigal et al , 2015 ; Fung et al , 2019 ). It has been shown that gland‐colonizing bacteria, not the bacteria colonizing the surface, induce the typical pathology associated with H. pylori infection, that is, stem cell expansion, gastritis, hyperplasia, and metaplasia—precursor lesions for gastric cancer (Howitt et al , 2011 ; Sigal et al , 2015 ; Fischer & Sigal, 2019 ; Liabeuf et al , 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Gastric stem cells promote inflammation and gland remodeling in response to Helicobacter pylori via Rspo3‐Lgr4 axis

et al. 2022

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Helicobacter pylori is a pathogen that colonizes the stomach and causes chronic gastritis. Helicobacter pylori can colonize deep inside gastric glands, triggering increased R-spondin 3 (Rspo3) signaling. This causes an expansion of the "gland base module," which consists of self-renewing stem cells and antimicrobial secretory cells and results in gland hyperplasia. The contribution of Rspo3 receptors Lgr4 and Lgr5 is not well explored. Here, we identified that Lgr4 regulates Lgr5 expression and is required for H. pylori-induced hyperplasia and inflammation, while Lgr5 alone is not. Using conditional knockout mice, we reveal that R-spondin signaling via Lgr4 drives proliferation of stem cells and also induces NF-jB activity in the proliferative stem cells. Upon exposure to H. pylori, the Lgr4driven NF-jB activation is responsible for the expansion of the gland base module and simultaneously enables chemokine expression in stem cells, resulting in gland hyperplasia and neutrophil recruitment. This demonstrates a connection between R-spondin-Lgr and NF-jB signaling that links epithelial stem cell behavior and inflammatory responses to gland-invading H. pylori.

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“…With deepened understanding of the molecular biological characteristics of gastric cancer, new gastric cancer treatment strategies were examined, and monoclonal antibody-targeted drug therapy and immunotherapy brought hope to patients with gastric cancer [ 4 ]. Tumor immunotherapy is a new kind therapy that used immunological principles and methods to activate a patient's own immune system and enhance the patient's anti-tumor immune response, which inhibits tumor growth [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Antitumor responses in gastric cancer by targeting B7H3 via chimeric antigen receptor T cells

Sun

et al. 2022

Cancer Cell Int

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Background Gastric cancer (GC) has a poor prognosis and limited therapeutic options. As a new promising cancer therapeutic approach, chimeric antigen receptor (CAR)-T cells represent a potential GC treatment. We investigated the antitumor activity of CAR-T cells target-B7H3 in GC. Methods In our study, expression of B7H3 was examined in GC tissues and explored the tumoricidal potential of B7H3-targeting CAR-T cells in GC. B7H3-directed CAR-T cells with a humanized antigen-recognizing domain was generated. The anti-tumor effects of this CAR-T cell were finally investigated in vitro and in vivo. Results Our results show that B7H3-directed CAR-T cells efficiently killed GC tumor cells. In addition, we found that B7H3 is correlated with tumor cell stemness, and anti-B7H3 CAR-T can simultaneously target stem cell-like GC cells to improve the treatment outcome. Conclusions Our study indicates that B7H3 is an attractive target for GC therapy, and B7H3 has high potential for clinical application.

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Stem Cells, Helicobacter pylori, and Mutational Landscape: Utility of Preclinical Models to Understand Carcinogenesis and to Direct Management of Gastric Cancer

Cited by 28 publications

References 160 publications

Helicobacter pylori und Magenkarzinom

Helicobacter pylori und Magenkarzinom

Gastric stem cells promote inflammation and gland remodeling in response to Helicobacter pylori via Rspo3‐Lgr4 axis

Antitumor responses in gastric cancer by targeting B7H3 via chimeric antigen receptor T cells

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