American scientists in experiments on mice prone to the development of melanoma, found that sterilization of females has no effect on the growth of tumors, but the castration of males increases the number of tumor foci in several times. Apparently, the fault of the immune cells neutrophils and testosterone — at least his injection this effect neutralizes. This same mechanism may explain why older men are ill with melanoma more often than women, and can also help to think of a more effective therapy for prostate cancer. Work published in the journal Nature Communications.
One of the most dangerous human cancers — melanoma — occurs in the population unevenly. Its prevalence is almost the same in men and women under 50 years, but after 50 men start to get sick almost twice as often than women. Moreover, gender is an important factor for the prediction of tumor development, regardless of other conditions — the size, location on the body, the degree of supply vessels and so on. However, it is still unclear exactly how gender may be associated with tumor development, which is not directly related to the sexual glands.
Markman Janet (Janet Markman) and her colleagues from the Medical center cedars-Sinai in Los Angeles suggested that the link may be the activity of the immune system. It is known that it in many ways regulate sex hormones: for example, estrogens inhibit inflammation, and androgens stimulate the healing of wounds. Probably, and antitumor activity of the immune system is also regulated differently in men and women.
To test this, the researchers used nokauti mice which turned off some genes control cell division — the ones which often have a mutation in people with melanoma. These animals more often than normal, developing tumors. Scientists estimate that lung nokauti females, melanoma occurs almost five times less frequently than males.
The researchers then conducted for males and females two types of operations: control (without damage of the internal organs) and removal of gonads. It turned out that females have a mouse none of the operations did not significantly affect the incidence of melanomas. But in males the effect was noticeable: after castration compared to the control operation, the number of melanomas in the lung has increased almost six times.
The researchers injected melanoma cells in the body normal and the operated mice and compared the strength of the immune response to the tumor. They found that within a tumor, the number of neutrophils — one of the groups of white blood cells responsible for innate immunity, have females and castrated males equally and a half to two times lower than that of ordinary males. To determine whether the number of neutrophils affects the growth of tumors, the researchers blocked their work using antibodies. In the end, the number of colonies of tumor cells in the lungs of females has not changed, and in males, increased in two times.
Thus, sex hormones affect the neutrophils, and they, in turn, to fight the tumor, but only in males. To find out whether to blame yourself or neutrophils hormones, the researchers conducted the experiment with bone marrow transplantation. Mice first underwent a bone marrow transplant own or someone else’s sex, and then infect them with melanoma. It was found that intact males had more neutrophils and fewer tumors than females, regardless of whose bone marrow they received. This means that the job of neutrophils is affected not their genetic gender, and hormonal environment.
When the researchers injected the castrated mice with testosterone, the effect of the operation has been neutralized: the tumor has grown no more, than in animals with intact testes. Conversely, when intact males were injected receptor blocker to testosterone, the number of tumors was doubled.
So, the authors confirmed that the loss of testosterone can affect the growth of tumors. Perhaps this explains why men after 50 die from melanoma more often than women. In addition, it can help to understand what is happening in the body of patients with prostate cancer. They often prescribe androgen deprivation (drugs that block the release or action of male sex hormones on the cells), so hormones are not stimulated tumor growth. But at the same time the deficiency of sex hormones is likely to reduce the activity of immune cells. And despite the fact that it is still unclear how neutrophils are involved in fighting the tumor, it can be assumed that patients with prostate cancer will survive better if deprivation therapy combined with immunotherapy.
Previously, scientists have discovered that testosterone makes men buy expensive items and prevents them critically evaluate the situation, and in women, by contrast, improves spatial reasoning. But is it true that men suffer illness heavier women, read our article “Immune gap”.