Oxidative Stress, Tumor Microenvironment, and Metabolic Reprogramming: A Diabolic Liaison

Figure 2

Oxidative stress in tumor microenvironment. Within microenvironment, oxidative stress can have intrinsic or extrinsic origin. Some stromal components can directly produce ROS. CAMs generate ROS through NOX2 activation and RNS through iNOS, while hypoxia produces oxidant species by deregulation of the complex III of mitochondrial electron transport or by NADPH oxidase activity [16, 42–46]. In response to extrinsic or intrinsic oxidative stress, CAFs became activated thus producing cytokines and proteases that affect tumour progression [41, 47, 48]. In addition, microenvironment or ageing-induced oxidative stress leads to secretion of “Senescent Activated Secretory Pathway” (SASP) by senescent fibroblasts affecting both stroma and cancer cells to promote cancer progression [49, 50]. Finally, cancer cells exacerbate oxidant environment by intrinsic production of oxidative stress through down-regulation of Jun D or enhanced of NOX-4, LOX-5 and COX-2 activity [41, 48, 51–53].