Diabetes mellitus contribution to the remodeling of the tumor microenvironment in gastric cancer

摘要

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.