Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

Abstract

Infection with Helicobacter pylori, a Gram-negative, microaerophilic pathogen often results in gastric cancer in a subset of affected individuals. This explains why H. pylori is the only bacterium classified as a class I carcinogen by the World Health Organization. Several studies have pinpointed mechanisms by which H. pylori alters signaling pathways in the host cell to cause diseases. In this article, the authors have reviewed 234 studies conducted over a span of 18 years (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020). The studies investigated the various mechanisms associated with gastric cancer induction. For the past 1.5 years, researchers have discovered new mechanisms contributing to gastric cancer linked to H. pylori etiology. Alongside alteration of the host signaling pathways using oncogenic CagA pathways, H. pylori induce DNA damage in the host and alter the methylation of DNA as a means of perturbing downstream signaling. Also, with H. pylori, several pathways in the host cell are activated, resulting in epithelial-to-mesenchymal transition (EMT), together with the induction of cell proliferation and survival. Studies have shown that H. pylori enhances gastric carcinogenesis via a multifactorial approach. What is intriguing is that most of the targeted mechanisms and pathways appear common with various forms of cancer.EMT refers to the process by which the mesenchymal phenotype is acquired by epithelial cells (ECs) mainly via the reduction of their intracellular adhesions and proliferative capacity (Figure 1.) [47].

Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches

“…EMT promotes the induction of the cancer stem cell (CSC) phenotype, which facilitates the progression of GC as well as further cellular stemness [ 31 ]. Both in vitro and in vivo studies showed that there is an interplay between EMT and inflammation since EMT facilitates the secondary release of pro-inflammatory cytokines; besides, chronic inflammation occurring in the GC microenvironment also triggers EMT [ 32 , 33 , 34 , 35 ]. Similarly, EMT and reactive oxygen species (ROS) formation are also associated with one another.…”

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

“…Among patients with GC, H. pylori is believed to be the major causation of this malignancy in approximately 92% of patients [ 10 , 11 ]. H. pylori infection enhances the progression of the epithelial–mesenchymal transition (EMT) that induces the oncogenic alterations within the gastric mucosa, constituting one of the hallmarks of gastric carcinogenesis [ 12 , 13 ]. Except for GC, H. pylori is responsible for the induction and progression of other gastrointestinal impairments and diseases, including gastritis, peptic ulcer disease, dyspepsia, or mucosa-associated lymphoid tissue lymphoma (MALT); contrarily, H. pylori is a protective factor against inflammatory bowel disease (IBD) and gastroesophageal reflux disease (GERD) [ 14 , 15 , 16 , 17 , 18 ].…”

Gastric carcinogenesis: a comprehensive review of the angiogenic pathways

“…Gastric carcinogenesis is a complex, multifactorial process that is primarily stimulated by chronic inflammation (induced by H. pylori infection in the majority of cases); however, other processes such as the epithelial-mesenchymal transition (EMT) or intensified angiogenesis play a crucial role in GC progression [19][20][21][22][23]. Angiogenesis is a physiological process of the formation of the new blood vessels from the already existing ones.…”