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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Diabetes mellitus contribution to the remodeling of the tumor microenvironment in gastric cancer
Armando Rojas, Cristian Lindner, Iván Schneider, Ileana Gonzàlez, Hernan Araya, Erik Morales, Milibeth Gómez, Nelson Urdaneta, Paulina Araya, Miguel Angel Morales
Armando Rojas, Cristian Lindner, Iván Schneider, Ileana Gonzàlez, Erik Morales, Paulina Araya, Biomedical Research Lab., Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
Hernan Araya, Milibeth Gómez, Nelson Urdaneta, Department of Clinical Sciences, Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
Hernan Araya, Milibeth Gómez, Nelson Urdaneta, Servicio de Oncología, Hospital Regional de Talca, Talca 34600000, Chile
Erik Morales, Servicio de Anatomía Patologica, Hospital Regional de Talca, Talca 34600000, Chile
Miguel Angel Morales, Department of Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Santiago 8320000, Chile
Author contributions: All authors contributed to the original ideas and writing of this paper; Rojas A designed the report and wrote the paper; Lindner C contributed art-work and data acquisition, drafting and revising the manuscript; Schneider I, Gonzàlez I, Araya H, Morales E, Gómez M, Urdaneta N, Araya P and Morales MA contributed data acquisition, drafting and revising the manuscript.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Armando Rojas, PhD, Full Professor, Biomedical Research Lab., Medicine Faculty, Catholic University of Maule, 3605 San Miguel Ave., Talca 34600000, Chile. arojasr@ucm.cl
Received: May 13, 2021
Peer-review started: May 13, 2021
First decision: June 5, 2021
Revised: June 10, 2021
Accepted: October 27, 2021
Article in press: October 27, 2021
Published online: December 15, 2021
Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial contribution of diabetes mellitus (DM) as a risk factor associated with increased cancer incidence and mortality in many human neoplasms, including gastric cancer (GC). DM is considered a systemic inflammatory disease and therefore, this inflammatory status may have profound effects on the tumor microenvironment (TME), particularly by driving many molecular mechanisms to generate a more aggressive TME. DM is an active driver in the modification of the behavior of many cell components of the TME as well as altering the mechanical properties of the extracellular matrix (ECM), leading to an increased ECM stiffening. Additionally, DM can alter many cellular signaling mechanisms and thus favoring tumor growth, invasion, and metastatic potential, as well as key elements in regulating cellular functions and cross-talks, such as the microRNAs network, the production, and cargo of exosomes, the metabolism of cell stroma and resistance to hypoxia. In the present review, we intend to highlight the mechanistic contributions of DM to the remodeling of TME in GC.
Core Tip: Compelling shreds of evidence support that diabetes mellitus (DM) is a crucial risk factor in human cancers. Due to its contribution to systemic inflammation, DM can sculpture the gastric tumor microenvironment through different mechanisms, which in turn, may generate highly malignant phenotypes in gastric cancer (GC). We herein discuss the contribution of DM in the remodeling tumor microenvironment in GC, which may then leads to more aggressive tumor phenotypes.
