In the field of oncology, a new concept is in the process of germinating: the internal architecture of tumor cells, in its finest lace, appears to be linked to the aggressiveness of tumors. The attention of researchers, in reality, is focused on a major building: the mitochondria or, more precisely, the stock of mitochondria that equips each cell. These microscopic “energy plants” in fact adopt, in cancer cells, varied morphologies and spatial distributions depending on the sources of nutrients they use. This is revealed by a study published on March 15 in the journal Nature.
Mitochondria play a crucial role in the processes that allow tumors to grow. It must be said that the energy needs of these tumors are very high: it is a question of feeding their unbridled growth. In 2016, a Belgian team showed that cancer cells can alternately feed on carbohydrates, lipids or proteins.depending on the oxygen level and the acidity of the surrounding environment. “Several studies have shown that flexible mitochondria, i.e. capable of using different substrates to produce energy, promote tumor growth”says Allan Pagano, lecturer at the Faculty of Sports Sciences in Strasbourg. When the environment becomes very acidic, cancer cells tend to abandon glucose – the main fuel of normal cells – to favor glutamine, an amino acid that makes up proteins. They also become able to use fatty acids to fuel their growth.
Two imaging techniques
In the new study, a team from the University of California, Los Angeles created genetically modified mice that carried specific mutations in their lung tissue. These rodents sometimes developed adenocarcinoma of the lung, sometimes squamous cell carcinoma of the lung. Then Mingqi Han, first author of the study, and her colleagues used two imaging techniques, positron emission tomography and volumetric electron microscopy, to draw high-resolution three-dimensional maps of the networks of mitochondria colonizing the cells of these tumors. Thanks to artificial intelligence, they were able to quantify the shapes and distributions of thousands of mitochondria, in hundreds of cells corresponding to all of these tumours.
The researchers discovered three types of mitochondrial frameworks. Type 1 mitochondria have an elongated shape, their internal membranes are relatively parallel to each other; and they are disseminated throughout the internal cell medium (“cytoplasm”). In addition, they are often associated with lipid droplets. ” These mitochondria are found more in cells that use diverse nutrient sources: fatty acids, glucose and glutamine.explains Christophe Grosset, director of research at Inserm at the Bordeaux Institute of Oncology. “These are more aggressive tumor cells”adds Raphaël Rodriguez, CNRS research director at the Institut Curie (Paris).
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