Bacterial Involvement in Progression and Metastasis of Adenocarcinoma of the Stomach
by
, and
Amanda D. Morgan
1, 
Kevin D. Seely
1,*,
Lauren D. Hagenstein
1,
Garrett M. Florey
2
and
James M. Small
3 1
College of Osteopathic Medicine, Rocky Vista University, Ivins, UT 84738, USA
2
College of Osteopathic Medicine, Rocky Vista University, Parker, CO 80134, USA
3
Department of Biomedical Sciences, Rocky Vista University, Parker, CO 80134, USA
*
Author to whom correspondence should be addressed.
Cancers 2022, 14(19), 4886; https://doi.org/10.3390/cancers14194886
Submission received: 13 September 2022
/
Revised: 26 September 2022
/
Accepted: 3 October 2022
/
Published: 6 October 2022
(This article belongs to the Special Issue Gastric Cancer Metastasis)
Simple Summary
Infectious bacteria influence primary gastric carcinogenesis, organotropism, and metastatic progression by altering the microenvironment at the primary and secondary tumors. Key species include Helicobacter pylori (H. pylori) and Mycoplasma hyorhinis (M. hyorhinis). Inflammation caused by H. pylori virulence factors, such as CagA, VacA, and oipA, disrupt epithelial integrity, which allows the primary tumor to progress through the metastatic process. Evidence supports the activation of aquaporin-5 by CagA-positive H. pylori infection, promoting epithelial–mesenchymal transition via the extracellular signal-regulated kinase/mitogen-activated protein kinase (MEK/ERK) pathway, thus laying the foundation for metastatic disease. M. hyorhinis has also been implicated in gastric neoplasia via β-catenin stabilization and subsequent activation of the WNT-signaling pathway, promoting gastric cancer cell motility and inciting cancer progression.
Abstract
Gastric cancer metastasis is a process in which the tumor microenvironment may carry significant influence. Helicobacter pylori (H. pylori) infection is well-established as a contributor to gastric carcinoma. However, the role that these bacteria and others may play in gastric carcinoma metastasis is a current focus of study. A review of the literature was conducted to elucidate the process by which gastric adenocarcinoma metastasizes, including its ability to utilize both the lymphatic system and the venous system to disseminate. Studies that investigate the tumor microenvironment at both the primary and secondary sites were assessed in detail. H. pylori and Mycoplasma hyorhinis (M. hyorhinis) were found to be important drivers of the pathogenesis of gastric adenocarcinoma by modifying various steps in cell metastasis, including epithelial–mesenchymal transition, cell migration, and cell invasion. H. pylori is also a known driver of MALT lymphoma, which is often reversible simply with the eradication of infection. M. hyorhinis has been implicated in gastric neoplasia via β-catenin stabilization and subsequent activation of the WNT-signaling pathway, promoting gastric cancer cell motility and inciting cancer progression. Fusobacterium nucleatum (F. nucleatum) and its association with worse prognosis in diffuse-type gastric adenocarcinoma are also reviewed. Recognition of the roles that bacteria play within the metastatic cascade is vital in gastrointestinal adenocarcinoma treatment and potential reoccurrence. Further investigation is needed to establish potential treatment for metastatic gastric carcinoma by targeting the tumor microenvironment.
