Cancer cells aren’t wasting glucose on purpose, they’re consuming it too quickly

A new study by researchers at the University of Washington at St. Louis Medical College reveals why cancer cells consume excessive amounts of glucose, but don’t always metabolize it efficiently. molecular cell.

Cancer cells craving glucose

Cancer cells require energy from glucose consumption to fuel their growth.yes many Because glucose is consumed by cancer cells, one cancer diagnostic approach, positron emission tomography (PET), uses imaging to probe the body for areas of excessive glucose consumption.

Interestingly, however, cancer cells do not use this excess glucose efficiently, releasing much of it as a waste product.This aspect of cancer metabolism has puzzled scientists for years. . “Tumors are puzzling because they grow rapidly and require a lot of fuel. It’s an incredibly interesting phenomenon named after Otto Warburg, who discovered it more than a century ago. . […] The biochemical logic for why cancer cells adopt such seemingly abnormal metabolic programs has been somewhat elusive. “An important step in advancing our understanding of cancer is to characterize these distinct metabolic signatures, which we hope will lead to new therapeutic insights.” Dr. Gary PattyMichael and Tana Powell Professor of Chemistry in the Arts and Sciences, Washington University, St. Louis Medical College.

Patty and colleagues metabolomicsA base approach to shed some light on this query. “Within a single experiment, we were able to measure the levels of thousands of metabolites from cancer cells. Overall, metabolomics can provide a fairly comprehensive picture of what is happening inside cancer cells,” explains Patti.

Cancer cells become ‘glucose saturated’

The research team utilized metabolomics techniques together with isotope tracers to overcome the current shortcomings of using metabolomics-based methods alone. “One of the current limitations of metabolomics is that it does not directly report where metabolites are located inside the cell,” explains Patti. This limitation is important because cells are made up of small compartments (organelles) that each have different functions within the cell. “To address this challenge in the present study, we took advantage of a clever and innovative approach developed by other researchers. Using special labels to ‘tag’ molecules at specific subcellular locations. By doing so, we were able to infer where the metabolites were in the cell,” adds Patti.

These methods have been applied to cancer cell lines that have been extensively studied by the National Cancer Institute and others.Each of these cell lines consumes glucose, but its efficiency is use It’s different. “We saw this as an opportunity to try to understand why some cancer cells waste more glucose than others,” says Patti.Ultimately, they found that cancer cells Until you can no longer metabolize glucose. Cancer cell lines vary in their ability to use glucose efficiently. “When pathways that use glucose efficiently saturate at their maximum, cells become more wasteful,” explains Patty. When the water fills up to the tub’s capacity, it begins to overflow the sides of the tub, wasting water. “When you limit the amount of glucose a cancer cell takes up, almost everything goes into the mitochondria,” Patti says. “However, as glucose consumption increases, the rate at which glucose-derived molecules move into the mitochondria cannot keep up.”

He said, “This is not a fundamentally new metabolic paradigm. Most cells prefer to oxidize the glucose in their mitochondria rather than excrete it as a waste product.” […] Our data suggest that cancer cells are no exception. They seem to follow the same biochemical patterns as other cells. ”

Targeting glucose metabolism may not be the most attractive approach to cancer treatment

What impact will this new discovery of cancer metabolism have on current cancer diagnostic and therapeutic efforts? He proposes to justify a ‘rethink’ of methods. ‘The best therapeutic targets are those specific to diseased cells. “It targets the cell wall of bacteria that does not. If glucose metabolism in tumors is indeed similar to healthy cells, it will be more difficult to pursue without potentially disrupting normal tissue function.” Previously, scientists proposed that limiting glucose uptake, either by pharmacological means or by reducing sugar consumption in the diet, could “starve” cancer cells. suggests that glucose metabolism as a therapeutic target for cancer therapy may not be as attractive as once thought.

To further develop their research, Patti and colleagues are trying to understand why some cancer cells have different glucose utilization capacities than others. It may have to do with the environment in which the tumor is located, such as the liver.It is also important to understand why cancer cells consume more glucose than they can efficiently use. Does it somehow support the growth of cancer cells, or is it functionally insignificant?” says Patti. “Answers to these questions may reveal new targets for therapy.”

Although many different cancer cell lines were investigated in this study, all type of cancer. “It is important that we continue to expand our analyzes to broaden the scope and include additional cancers,” she concludes Patti.

Professor Gary Patti was talking with Molly Campbell, Senior Science Writer at Technology Networks.

reference: Wang Y, Stancliffe E, Fowle-Grider R et al. Saturation of her NADH shuttle in mitochondria promotes aerobic glycolysis in proliferating cells. Mole. cell. 2022. Doi: 10.1016/j.molcel.2022.07.007.