Cancer spreads through the nerves
Nerves help cancer grow
Kirill Stasevich, Science and Life (nkj.ru )
A cancerous tumor does not exist by itself, but is surrounded by other cells with which it constantly interacts and which it tries to make work for itself. In particular, connective tissue fibroblast cells, which give collagen and heal wounds, once near the tumor, begin to help it grow and seize new territories. The tumor also manages to deceive the immune system, whose task, generally speaking, is to destroy malignant cells – the tumor makes it so that the immune system does not see it. Moreover, some immune cells even begin to work on the tumor – last year we told how an escort of immune cells helps cancer to metastasize.
And then there are the neurons. Again, last year we wrote about how cancer connects to the neurons of the brain – malignant cells intercept their neurotransmitters from the nerves in order to grow themselves and spread further through the brain. But it's not just brain tumors that benefit from neurons. It is known that if there are a lot of nerve fibers in the environment of prostate cancer, then such a cancer will be more aggressive, it will increase in size faster and spread metastases more actively. Obviously, nerve cells in general tend to help malignant tumors. But what kind of mechanism works here?
Researchers from The M. D. Anderson Cancer Center studied the behavior of a head and neck tumor that develops in the tissues of the larynx, pharynx, nose or sinuses, oral cavity or from the tissues that surround them. In many cases, tumors have mutations in the TP53 gene, which encodes the p53 protein. This is one of the most famous antitumor proteins: p53 monitors the integrity of DNA, and when too much damage accumulates in it – which threatens the cell with becoming cancerous – it launches a program of cellular self-destruction. It is clear why in many tumors (not only in tumors of the head and neck) the p53 protein gene is corrupted.
Researchers from The M. D. Anderson Cancer Center studied the behavior of a head and neck tumor that develops in the tissues of the larynx, pharynx, nose or sinuses, oral cavity or from the tissues that surround them. In many cases, tumors have mutations in the TP53 gene, which encodes the p53 protein. This is one of the most famous antitumor proteins: p53 monitors the integrity of DNA, and when too much damage accumulates in it – which threatens the cell with becoming cancerous – it launches a program of cellular self-destruction. It is clear why in many tumors (not only in tumors of the head and neck) the p53 protein gene is corrupted.
On the other hand, in some patients the same type of tumor appears, despite the working p53. Comparing head and neck tumors in experimental mice and comparing medical statistics, the researchers found that more nerve fibers appear around tumors with mutant p53, and the more nerve fibers accompany the tumor, the worse the clinical prognosis. Cancer cells, and not only cancer cells, communicate with each other using microscopic bubbles-vacuoles containing different molecules. Cancer cells in such bubbles send out molecular instructions that can turn a completely healthy cell into a malignant one.
An article in Nature (Amit et al., Loss of p53 drives neuron reprogramming in head and neck cancer) states that there was no molecule called miR-34a in microbubbles from tumor cells with mutant p53. This is one of the microregulatory RNAs – small RNA molecules that do not encode any proteins, but instead suppress protein synthesis on other, large matrix RNAs. It is known about miR-34a that it has antitumor properties: it controls cell division. But how is it related to the neurons surrounding the tumor?
The nerve cells that surround a tumor with mutant p53 are different from the nerve cells that surround a tumor with normal p53. In the first case, these are mainly adrenergic neurons that use norepinephrine to transmit a signal. When mice with a tumor in which p53 did not work were given the drug carvedilol, which blocks adrenoreceptors, tumor growth slowed down. As a result, the following picture turned out: a tumor with a non-functioning p53 sent molecular messages around itself, forcing nerve cells to switch to norepinephrine signals. (And the molecular parcels turned out to be so harmful because they did not contain the antitumor molecule miR-34a.) Why exactly such neurons stimulate tumor growth is still unclear, but already now we can think about how to suppress tumor growth by acting on the surrounding nerve cells.
The same carvedilol is usually prescribed to lower blood pressure, but there is evidence that it simultaneously reduces the likelihood of cancer. Perhaps he himself or similar drugs could be an addition to conventional antitumor drugs. Mutations in the TP53 gene are present in 60% of cases of colon cancer, 50-80% of lung cancer and 95% of ovarian cancer. It is possible that all these tumors also receive bonuses from adrenergic neurons, which means that such a tool that would suppress the growth of tumors by disconnecting them from neurons would be very, very useful in everyday clinical practice.
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