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