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

Mitochondrial dysfunction in breast cancer cells prevents tumor growth

“…We and others have now shown that genetic changes in epithelial cancer cells (conveyed by either oncogenic mutations or by loss of tumor suppressor function) induce the production of hydrogen peroxide by cancer cells. [20][21][22] Hydrogen peroxide released from cancer cells then functions to fertilize their surrounding microenvironment via the induction of oxidative stress in tumor stromal cells, especially cancer-associated fibroblasts. [20][21][22] in human fibroblasts.…”

“…[20][21][22] Hydrogen peroxide released from cancer cells then functions to fertilize their surrounding microenvironment via the induction of oxidative stress in tumor stromal cells, especially cancer-associated fibroblasts. [20][21][22] in human fibroblasts. To understand how fibroblasts overexpressing UCP1 promote tumor growth, we explored the hypothesis that increased tumor growth is due to the onset of a catabolic stromal phenotype, which can support the anabolic growth of cancer cells via stromal-epithelial metabolic coupling.…”

Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis

“…35 This ROS production was reduced to baseline levels by co-incubation with extracellular catalase, identifying the predominant ROS species as hydrogen peroxide. 35 In contrast, by day 5, most of the ROS production occurred Figure 2. transcriptional overlap between Alzheimer brain disease and the breast cancer tumor stroma: association with metastasis.…”

“…23,24,35 This results in the production of L-lactate in cancer-associated fibroblasts, via aerobic glycolysis. Then, these fibroblasts secrete L-lactate as a waste product and cancer cells use L-lactate as "fuel" to burn in their mitochondrial TCA cycle, via oxidative phosphorylation.…”

“…[32][33][34] Several independent lines of evidence now suggest that hydrogen peroxide may function as the "fertilizer" in this process, by driving accelerated aging, DNA damage, inflammation and cancer metabolism. [35][36][37][38][39] Catalase is one of the major enzymes that detoxifies hydrogen peroxide in the body, functioning as a powerful catalytic anti-oxidant. Catalase converts hydrogen peroxide to water and oxygen.…”