Nicotine helped lung cancer to metastasize to the brain

Smoking and other ways of using nicotine increase the risk of lung cancer metastases in the brain. Although by itself, nicotine is not a carcinogen, it preprogrammed immune cells of the brain, not allowing them to effectively fight with malignant tumors. As noted by the researchers in an article for the Journal of Experimental Medicine, the discovery shows that even replacement therapy type of nicotine patches and electronic cigarettes deadly for patients with lung cancer.

40 percent of people suffering from lung cancer, develop metastases in the brain. The average life expectancy of these patients is just six months. Unfortunately, it remains unclear what factors stimulate the penetration of malignant cells into the brain. Many experts suspect that the cause may be Smoking, however, although the relationship between this habit and the development of lung cancer is proven, its role in the formation of metastases has not been studied.

To understand this question decided the researchers, led by Konosuke of Watabe (Kounosuke Watabe) from the Medical school of Wake forest University. At the first stage they examined 281 patients with lung cancer, which has metastasized to the brain. It turned out that those who continued to smoke even after diagnosis, the risk of penetration of the disease in the brain was much higher. In contrast, patients who never smoked or got rid of this habit, the less experienced the emergence of metastases.

As shown by the analysis of the structure of the brain of smokers in areas the spread of metastases is the standard of microglia phenotype M1 is dominated by M2. This microglia suppressed inflammatory processes and thereby helped the tumors to survive and grow. In addition, cells of type M2 has ceased to absorb the malignant cells.

The researchers suggested that the shift in the work of the microglia was triggered by the nicotine. To test this idea, they conducted an experiment with laboratory mice. Animals transplanted lung cancer cells, and then every three days injected dose of nicotine at the rate of one milligram per kilogram of body weight. As a result, individuals receiving injections, more often formed metastases of lung cancer in the brain. As in humans, in rodents on the affected areas of the brain dominated microglia type M2. Interestingly, the risk of metastasis in the bone nicotine had no effect.

Additional experiments with cell cultures have confirmed that nicotine does not increase the growth rate of malignant cells, but changes the phenotype of microglia from M1 to M2, affecting a number of genes via nicotinic acetylcholine receptors. As a result, she loses the ability to restrain cancer metastasis.

Then the team members tried to find a compound that could neutralize the effect of nicotine. Viewing a library of natural compounds, they chose 103 molecules candidate is able to cross the blood-brain barrier. The most promising of them was a substance called parthenolide, a sesquiterpene lactone from the medicinal plants of the maiden tansy (Tanacetum parthenium). In experiments with cell cultures and mice parthenolide not only reversed the transformation of microglia M1 to M2, but also contributed to the reduction of metastases. The researchers hope that this molecule will form the basis of new drugs for treatment of advanced stages of lung cancer.

The obtained results open up new perspectives for cancer therapy. As the authors point out, they once again remind us of the dangers of nicotine for patients with lung cancer. Moreover, the threat is not only Smoking, but also the use of proxy tools such as nicotine patches and electronic cigarettes.

Smoking not only increases the risk of malignant tumors in the brain, but also harm mental health. As shown by a study by British geneticists, between Smoking and risk of schizophrenia and depression there is a causal relationship. Schizophrenia smokers get sick 2.27 times more often and depression — 1.99 times more often.

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