Major discovery: Tumor metabolism is slower than expected

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Major discovery: Tumor metabolism is slower than expected

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Major discovery: Tumor metabolism is slower than expected, saving energy for growth and metastasis.

A person’s food, clothing, housing and transportation are inseparable from money, and the same is true for cells, except that the “money” here is the unique “energy currency” in the organism – adenosine triphosphate ( ATP) .

It is generally recognized that the rapid proliferation of cancer cells consumes a lot of energy and seizes a lot of resources, which will cause normal cells to fall into the dilemma of “no money to use”.

In other words, if normal cells are compared to ordinary people who live frugally, then cancer cells are undoubtedly a profligate “prodigal”.

Unexpectedly, in a new study, Princeton researchers have demonstrated for the first time that the opposite is true — that primary solid tumors produce ATP much more slowly than normal tissue, and that this indolence may help tumors Conserves energy for growth and transfer.

The research was published in the journal Nature on February 1, 2023 under the title: Slow TCA flux and ATP production in primary solid tumors but not metastases .

In cells, ATP can be produced through glycolysis and mitochondrial aerobic respiration.

Glycolysis is a glucose catabolism pathway that produces 2 molecules of ATP for every molecule of glucose consumed.

In contrast, mitochondrial aerobic respiration is undoubtedly more efficient, producing 14.5 molecules of ATP for every molecule of glucose consumed.

In the 1920s, German physiologist Otto Warburg discovered that tumors exhibit more glycolysis than other tissues, even in the presence of oxygen , a phenomenon known as the Warburg effect .

So, why do tumor cells abandon the high-efficiency mitochondrial aerobic respiration and choose the less efficient glycolytic metabolism? Is it true that “to be rich is to be willful”?

In this latest study, the research team developed and validated a strategy to measure mitochondrial tricarboxylic acid cycle (TCA cycle) flux in normal and tumor tissues of mice by injecting an isotopic tracer followed by mass spectrometry and by The resulting metabolite labeling data is used for quantitative modeling to track metabolic rates in normal and tumor tissues.

Determination of Metabolic Rates in Normal and Tumor Tissues of Mice by Isotope Tracer Method

By measuring the rate of the glycolytic or TCA cycle pathways, the research team calculated the rate of ATP production for each tissue or tumor type, thereby measuring the rate of energy production in different tissues in living animals.

They were surprised to find that despite the relatively high rate of glycolysis in tumors, the TCA cycle of primary solid tumors was significantly inhibited, and their ATP was still mainly produced by mitochondrial aerobic respiration.

Thus, overall, the rate of total ATP production in solid tumors is significantly lower than in healthy tissues . Additionally, the team found that metastatic tumors produced and consumed more energy than primary tumors , but even then only at levels comparable to healthy tissue.

Tumors have lower metabolic rates compared to healthy tissue

These new findings raise new questions: How do tumor cells sustain rapid proliferation if they are relatively slow to make and use energy?

Tumors often fail to perform the normal functions of the tissue from which they originated.

For example, one of the main functions of a healthy pancreas is to produce digestive enzymes, but pancreatic tumor cells do not produce these enzymes, and their production and secretion are often energy-intensive.

Thus, by avoiding these normal tissue functions, tumor cells conserve large amounts of ATP that can then be used for cell proliferation.

Tumors produce ATP slower than healthy tissue

Professor Joshua Rabinowitz , the corresponding author of the paper, said: From the facts, this is very reasonable, because most cancer cells face a harsh metabolic environment, such as lack of vasculature to transport nutrients, so they are forced to use less “money”. “Do more.

Metastatic tumors have higher metabolic rates than primary tumors

Altogether, this Nature paper is the first to quantify tumor energy production in living animals and demonstrates that primary tumors metabolize energy at a slower rate than most normal tissues.

This new discovery breaks the previous cognition and shows that cancer cells are actually well versed in the way of frugality . Clear (one-hearted proliferation) .

Tumors downregulate energy-intensive tissue functions

Not only that, this new discovery provides new insights into anti-tumor treatment research, such as ” cancer starvation therapy “.

From the point of view proposed in this paper, cancer cells are more hungry than we thought, and want to “starve “die” tumor cells may end up starving themselves first .

Furthermore, this study also points out that metastatic tumors consume more energy than primary tumors , and perhaps targeting the nutritional requirements of metastatic tumors could be a promising strategy to combat this deadly stage of cancer.

Paper link :
https://www.nature.com/articles/s41586-022-05661-6

Major discovery: Tumor metabolism is slower than expected

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