For over a century, cancer cell metabolism has been viewed as something of a paradox. New work from researchers at Washington University in St. Louis shows that it might not be such an anomaly after all. The study is published Aug. 15 in Molecular Cell.
Glucose, a common sugar in food, is one of the most important nutrients in the body. Cancer cells tend to consume it at an astounding pace. At first glance, that seems to make good sense because cancer cells have a lot of synthesis to do. After all, as tumors grow rapidly, each cell has to replicate its entire contents.
But here’s the catch. Cancer cells don’t use the glucose very efficiently. Instead of sucking all of the energy they can out of glucose, they release most of it as a waste material.
“To extract the maximum amount of energy from glucose, cells must transport its transformation products into mitochondria,” said Gary Patti, the Michael and Tana Powell Professor of Chemistry in Arts & Sciences and of genetics and of medicine at the School of Medicine. Patti, a member of Siteman Cancer Center at Barnes-Jewish Hospital and the School of Medicine, is senior author of the new study.
All sorts of explanations have been offered as to why cancer cells might want to be wasteful with their glucose. However, Patti and his team contend that these rationalizations may be unnecessary. In the end, cancer metabolism may not be as unusual as scientists thought.
Cancer cells really do want to metabolize glucose in their mitochondria, and they do so. Until they can’t.
In other words, cancer cells only waste glucose away because transport into mitochondria is too slow.
Imagine a bathtub faucet that is spitting out water faster than the drain can remove it. Eventually, the water overflows onto the floor.
In this study, the researchers combined metabolomics with stable isotope tracers. This allowed them to tag different parts of glucose so that they could track it inside of cells, watching the speed at which things entered mitochondria or were excreted from cells. That is how the scientists discovered that the normal pathways for transporting fuel were getting outpaced, or saturated, in cancer cells.
The rate at which tumors consume glucose has been exploited by doctors in the clinic for decades as a way to diagnose cancer and identify its stage. It also has led some to believe that limiting glucose uptake with drugs or by eating a sugar-free diet might “starve” the cancer cells to death.