Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect

• DOI: 10.4161/cc.10.15.16585
• Publication Date: 2011-08-22T17:04:13Z
• Authors: Ubaldo E. Martine...; Zhao Lin; Casey Trimmer; Neal Flomenberg; Chenguang Wang; Stephanos Pavlides; Richard G. Pestell; Anthony Howell; Federica Sotgia; Michael P Lisanti
• Keywords: Warburg Effect; Anaerobic glycolysis

Previously, we proposed that cancer cells behave as metabolic parasites, they use targeted oxidative stress a "weapon" to extract recycled nutrients from adjacent stromal cells. Oxidative in cancer-associated fibroblasts triggers autophagy and mitophagy, resulting compartmentalized cellular catabolism, loss of mitochondrial function, the onset aerobic glycolysis, tumor stroma. As such, produce high-energy (such lactate ketones) fuel biogenesis, metabolism We have termed this new energy-transfer mechanism "reverse Warburg effect." To further test validity hypothesis, here used an vitro MCF7-fibroblast co-culture system, quantitatively measured variety parameters by FACS analysis (analogous laser-capture micro-dissection). Mitochondrial activity, glucose uptake, ROS production were with highly-sensitive fluorescent probes (MitoTracker, NBD-2-deoxy-glucose, DCF-DA). Interestingly, using approach, directly show initially secrete hydrogen peroxide then neighboring fibroblasts. Thus, is contagious (spreads like virus) propagated laterally vectorially Experimentally, reduces increases become more dependent on glycolysis. Conversely, co-cultured significant corresponding reductions both uptake GLUT1 expression. Pre-treatment co-cultures extracellular catalase (an anti-oxidant enzyme detoxifies peroxide) blocks stress, potently induces death cells, likely via starvation. Given largest suggest PET imaging human tumors, Fluoro-2-deoxy-D-glucose (F-2-DG), may be specifically detecting stroma, rather than epithelial