Cienciaes.com: The perversity of tumor exosomes

by time news

2015-08-09 22:14:03

It is possible that we feel overwhelmed by the amount of knowledge that Humanity, thanks to the scientific enterprise, has been accumulating about Nature. Knowledge is already of such magnitude that it may seem to some that we know everything. However, far from this, science continues to reveal new and increasingly fascinating processes. And not only does he reveal them, but he studies them tirelessly to understand how they work and also find out if they can be useful to us in some way.

Surprising, without a doubt, is the discovery of the so-called exosomes, or extracellular vesicles. These are corpuscles of only 30 to 100 nanometers in diameter, that is, comparable in size to that of viruses, which is 20 to 300 nanometers (a millimeter has one million nanometers). As their name indicates, exosomes are vesicles secreted outside by cells. Initially discovered in 1987, no one gave them much importance until, in 2007, researchers at the University of Gothenburg, in Sweden, discovered that these vesicles carried an interesting cargo inside, composed of an evolutionarily conserved set of proteins (i.e. similar in different related species), as well as messenger RNA and interference RNA, and even DNA fragments.

The presence of proteins and genetic material in exosomes suggested that perhaps they could serve as a mode of transport for these materials between neighboring, or not so neighboring, cells. The presence of exosomes was detected in major body fluids, including blood, indicating that they could transport their cargo to distant sites in the body. Indeed, other studies indicated that exosomes produced by some cells could be taken up by others, and that messenger and interference RNAs affected the production of proteins by the cell that had taken them up.

Exosomes were thus revealed as a means for one cell to affect the behavior of others, in this case also providing the materials required to do so, without depending on the recipient cell to manufacture them itself. This last situation is what occurs, for example, when hormones act. These only give orders to cells to start making other proteins, or to turn their own genes on or off and thus change their function. Exosomes, however, would not work in the same way.

Messages from abroad

The above considerations opened the door to the possibility that exosomes could serve as a way for the cells that produced them to signal to nearby cells that they should adapt to the changes in the environment that the former had detected. It would be as if the cells that first detect a change, or a threat, produced exosomes loaded with molecular tools that help their colleagues, as well as themselves, cope with the situation. Indeed, a study published in 2010 revealed that tumor cells subjected to low levels of oxygen secreted exosomes that could stimulate the formation of new blood capillaries or favor metastasis, that is, they either increased the supply of oxygen or stimulated other cells. to escape from the low oxygen environment and migrate to another more favorable place where they can continue growing.

One problem with these studies, however, was that they had been performed only on cells grown in the laboratory. Although these types of studies are important in revealing what can or cannot happen in biology, they are not always indicative of what happens in the living animal. In this sense, it remained unknown whether exosomes secreted by some cells of a tumor could affect other tumor cells to form metastasis or change their biological behavior in some other way.

Experiments on living beings are always technically much more complicated than those carried out with cultured cells. Some researchers had injected mice with exosomes purified from those produced by tumor cells in culture to study their effects, but this is not indicative of what happens with the generation and incorporation of exosomes inside a tumor, in which Cells may be exchanging exosomes with each other depending on several factors, such as the presence of nutrients, oxygen levels, etc., which can modify their behavior and malignancy.

Now, a group of researchers from several Dutch research centers are developing a new method based on modern molecular biology techniques. This method allows them to load exosomes produced by tumor cells with a protein capable of activating a particular gene in the cells that take them up. The activity of this gene thus becomes a sure indication that a cell has taken up exosomes, which now makes it possible to study what changes occur in its behavior. Likewise, researchers use a microscopic technique that allows them to visualize the movement of exosomes inside a tumor.

Scientists thus discover that the most malignant tumor cells produce exosomes that are taken up by the less malignant ones, which increases their capacity to form metastases, that is, making them as malignant as the former. This interesting discovery, published in the journal Cell, as so many times, opens the door to the possibility of intervening on this mechanism with new drugs that block the generation of exosomes in tumor cells and thus prevent the spread of metastatic tumor behavior. the most dangerous for the lives of patients.

Referencia: Zomer et al., In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior, Cell (2015),

#Cienciaes.com #perversity #tumor #exosomes

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