The exploiting tumor
Cancer cells make healthy ones work for themselves
A cancerous tumor is an insidious thing in itself, as it is formed from our own cells. But it can also affect healthy tissues, changing their metabolism. So one of the directions of anti-cancer therapy may be intervention in the processes occurring outside of malignant cells
The tumor can grow very quickly depending on the intake of nutrients to it, primarily glucose monosaccharide. The fact is that cancer cells need a huge amount of glucose, which serves as their main energy substrate: the level of glycolysis (glucose breakdown) in tumor tissue is tens and hundreds of times higher than in normal ones.
This phenomenon, known since the 1970s, is named after its discoverer, the Warburg effect. Now it is the basis of a diagnostic test for cancer: glucose labeled with radioactive isotopes is injected into patients and its path in the body is tracked using positron emission tomography.
But how can this "energy" need of the tumor affect other, healthy tissues of the body? To test this, scientists from Washington University in St. Louis (USA) we studied the metabolism of healthy and cancerous tissues in small freshwater danio-rerio fish, which developed melanoma as a result of mutation.
Article by Naser et al. Isotope tracing in adult zebrafish reveals alanine cycling between melanoma and liver is published in the journal Cell Metabolism.
It turned out that melanoma cells consume about 15 times more glucose than healthy tissues, but the glucose level in the blood of fish remained constant. The latter is clear: the glucose level in the blood of a healthy individual, including a human, is strictly controlled, and in case of a shortage, glucose is synthesized in the liver.
In order to study the low-molecular metabolic profiles in the body of fish, their feeds were labeled with isotopic labels. It turned out that the amino acid alanine is derived from melanoma cells, which is absorbed by the liver, where it is used for glucose synthesis. That is, in this case, the liver helps the tumor to develop! And experimental suppression of this "alanine cycle" helped to reduce the tumor load in fish.
Figure from the article by Naser et al. – VM.
The removal of alanine from the tumor is facilitated by the activation of the BCAT1 gene in cancer cells, which encodes an enzyme involved in the degradation of branched chain amino acids. BCAT1 hyperactivity has already been detected in many types of tumors, and melanoma cells in both zebrafish and humans are no exception.
Scientists have found disorders and changes in metabolism in most healthy tissues in sick fish, which suggests that the tumor can have a systemic effect on the entire body. And, as we can see, in some cases they work for the benefit of cancerous tissues, which opens up a new direction in antitumor therapy.
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