Metabolic Heterogeneity in Human Lung Tumors
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Non-small cell lung cancer (NSCLC) is heterogeneous in the genetic and environmental parameters that influence cell metabolism in culture. The study also provides insight into a long-standing misconception about cancer metabolism.
For nearly a century, researchers had relied upon the idea that a metabolic switch takes place when a benign tumor becomes cancerous, whereby oxidative metabolism is turned off and glycolytic metabolism is turned on. While enhanced glycolysis and glucose oxidation were common among these tumors, authros observed evidence for oxidation of multiple nutrients in each of them, including lactate as a potential carbon source.
To determine how differences in blood flow might affect tumor metabolism, the research team measured the amount of blood flowing into various parts of tumors in patients by using a suite of advanced imaging techniques. To pinpoint which regions of the tumors needed to be sampled during the removal process based on the results of the imaging investigation. Following surgical removal of the tumors, the research team performed fragment-by-fragment metabolic flux analysis to examine the metabolic changes that occurred. The study found that there is no switch from one source of energy to the other; instead, both types of metabolism increase when a benign tissue becomes cancerous.
The study also suggests that glucose is not the sole nutrient that solid tumors consume for energy, but is one of many nutrients, a finding that potentially expands the number of metabolic pathways that could be targeted to fight a tumor's progression.
In addition, it appears that the metabolic preference of tumors that is determined by their genetics can be overridden by the cellular environment. Tumors -- and even different regions of the same tumor -- that receive a lot of blood flow were found to use many different nutrients for energy. Tumors and different areas of the same tumor that receive less blood flow were more likely to use glucose as the primary fuel.