Cells gone mad

Tumor stem cells

Evgeny Cheval, Post-science

Oncological diseases are one of the main causes of death, and the attention of scientists is focused on this problem extremely strongly. In order to cure a tumor, we need to know where to strike to kill it. In fact, there is a constant race – researchers need to learn something new in order to be able to treat oncological diseases more effectively.

Periodically, facts appear that radically change our view of how tumors arise, form and grow. And this forces scientists to look for new cancer treatments.

One of these discoveries is the discovery of tumor stem cells, which was made in 1991. To understand what it is, you must first understand the structure of normal tissues. Normal tissues are formed by cells and come in two types. There are tissues where cells exist throughout life, they do not divide, they do not multiply. The most famous example is brain cells, neurons. The number of them in the adult body does not increase, but gradually decreases, because neurons die with age.

There are also other tissues in which cells work "to wear out" and die quickly. Why is that? For example, because they can exist in unfavorable conditions, like intestinal epithelial cells that live in a very aggressive environment. Intestinal epithelial cells in working condition (that is, when they are differentiated to perform their function and work) live 3-5 days. They should be replaced by new cells. Cells in such tissues are constantly being updated, and in order for this update to occur, the tissues are arranged as follows – they have several types of cells.

The first type of cells are stem cells, such "lazy cells". They sit, rarely divide, and very "take care" of themselves so that the cell is not damaged. The body tries to hide them in some secluded places. Stem cells do not divide often on purpose – it is easy to damage the cell during division. Such a cell should last a lifetime, because it will ensure the renewal of those cells that are doomed to death, such as intestinal epithelial cells. Sometimes a stem cell divides, and some of its descendants remain in the state of a stem cell, and some give rise to a renewing population.

These descendants (the second part) begin to divide intensively, and when several rounds pass, division stops, slows down, and the cell begins to differentiate, that is, acquires features of structure and functioning that allow it to effectively perform the function for which it was created. After that, the cell works for a while, while this work is effective, and then it dies. And this is an actively updating population.

What are tumor cells? These are cells that are "crazy", they behave incorrectly, not in the way the body needs. There is a complex structure described above, when the body controls that you do not have too many intestinal epithelial cells formed, and not too few formed, which is also bad. And a tumor is cells that have gone crazy.

It can be assumed that all tumor cells are equally capable of dividing and each of them can give a new tumor. Is it so? At some point it turned out that there was no. The work was done, which took decades and required very hard preparation. As a result of the research, it turned out that the cells in the tumor are not the same. There may be different proteins on their surface membrane, and different cells can be selected from these proteins with the help of antibodies. And in one of the tumors (this was first established in chronic myeloid leukemia), a small group of cells was found, less than 0.1% of the total number, with certain characteristics that slightly differed from the bulk of the cells.

Then a very simple experiment was set up: these cells were injected into mice and checked whether they formed a tumor or not. The remaining cells, of which 99.9%, were also injected by mice. And they found a very strange thing: a tumor is formed from these few cells, but a tumor is not formed from the bulk of the cells. An idea arose: maybe these few cells are just a complete analogue of stem cells that are responsible for the renewal of this tissue. Yes, it is a tumor, but it is also a tissue, and it is also heterogeneous in structure – it has cells that are responsible for renewal, and the bulk, the mass of the tumor in this case, which is not able to fully reproduce the tumor. It was a very unusual thought, and for a long time scientists just checked, took various tumors, looked for confirmation. In many tumors (not all), indeed, such a device was discovered: the cells are heterogeneous, some of them (they were called tumor stem cells) are responsible for the renewal of the tumor, and the bulk simply exists.

Why is this so important? It would seem that they have discovered a parameter by which tumors are a bit like normal tissues ... after all, they also originate from normal tissues. And that's why it's important: as soon as people came to terms with the fact that tumor stem cells exist, they realized the fact that we are now treating tumors incorrectly. When a doctor treats a tumor, his main task is to reduce the mass of the tumor. When a scientist is looking for a cure in order to treat a tumor later, he looks, first of all, to reduce the mass of the tumor. And what happens at the level of tumor stem cells? Maybe by reducing the mass of the tumor, we kill the main number of cells, but do we kill stem cells at the same time or not? After all, if we don't kill them, a new tumor will grow from the stem cells, and a relapse is inevitable. At the same time, it became clear how to treat. It is necessary to do so in order to directly hit the tumor stem cells. If we hit them, there will not even be a need to remove the rest of the tumor – we will destroy only a small population, a fraction of a percent, but the rest of the tumor is supported by tumor stem cells... the tumor itself will die, it will melt. And at some point, scientists realized that they had to look for drugs, ways to destroy tumor stem cells directly.

So far it looks fantastic, although the first work on mice is already underway. There is hope that it will be possible to destroy tumor stem cells. So far we know too little. We know that they exist, we know about some of their features, sometimes we know where they come from. But as we learn more, there will be new medicines, there will be ways to cure those patients who are still incurable.

Author –
Candidate of Biological Sciences, Senior Researcher at the A.N. Belozersky Research Institute of Physico-Chemical Biology of Moscow State University

24.04.2013