JEM: Cracking the mystery of smoking promotes lung cancer cells to get into the brain! Scientists have found that nicotine alters the properties of small glial cells, making the brain suitable for cancer cells to grow.

!---- lung cancer is one of the most common cancers and prone to metastasis, with 10 to 36 percent of lung cancer patients estimated to have brain metastasis, a number that may still be underestimatedbrain metastasis occurs, the patient's median survival is usually not more than 6, mainly because the brain structure is complex and special, drug delivery is difficult, surgery risk is large, although the new radiotherapy in recent years has been found to help control the brain transfer, but the effect is not very good, and radiotherapy will also kill normal nerve cells, the impact on the patient's lifetherefore, finding the cause of brain metastasis and preventing it is one direction that many researchers are trying to dorecently published in the Journal of Experimental Medicine, researchers at Wake Forest University Baptist Medical Center show that smoking is one of the reasons for lung cancer's transfer to the brainPhoto Their experiments from pexel.com found that nicotine in cigarette smoke can cross the blood-brain barrier into the brain, prompting macrophages in the brain, small glial cells, to alter phenotypes, increase the secretion of growth-promoting and chemators, and promote the formation and development of metastases, nicotine inhibits the ability of small glial cells to eat, preventing them from processing tumor cells, however, the researchers identified a compound extracted from small chrysanthemums, the small chrysanthemum, which prevents nicotine from altering the phenotype of small glial cells, thereby inhibiting brain metastasissmoking has been shown by many studies to be one of the main risk factors for lung cancer, and previous correlation studies have found that smoking is associated with a rapid development of brain metastasis in lung cancerthis time, the researchers also analyzed the relationship between brain metastasis and smoking in 281 patients with advanced lung cancer, with significantly higher rates of brain metastasis in patients who had no smoking habits and those who had quit smoking, and smoking was associated with lower survival rates and overall survival rates for cerebral palsy progressionA: The incidence of brain metastasis (black) in non-smoking, smoking cessation and persistent smoking patients (black) vsB, C: Non-progressive survival of smokers (red) and total survival compared to the brain metastasis in smoking patients, the number of small glial cells increased significantly, and most were M2Given studies a few years ago have shown that the activation of small glial cells is associated with the progression of brain tumors, and that nicotine, the main part of cigarette smoke, binds to the nicotine-type acetylcholine (nAch) receptor, which is also widely expressed in small glial cellsthe researchers speculated that people with lung cancer who smoked were more likely to have brain metastasis, which may be nicotine and glial cellssmall glial cells are activated in two types, one is classic (M1) and one is alternative (M2)M1 small glial cells can secrete tumor necrosis factors such as alpha and leukocyte interleukin-1 beta, initiate inflammatory reactions, causing apoptosis, while M2 mainly secretes endothelial growth factors and conversion growth factor-beta, etc., to promote angiogenesis and inflammation repairnormally, two types of small glial cells are dynamically balancedBut for now, the presence of nicotine seems to have upset their balance researchers found that small glial cells express high levels of nAch receptor alpha4 beta2, the most sensitive receptor for nicotine in the brain in two models of lung cancer, the researchers injected them with nicotine, and the incidence of brain metastasis increased significantly in both lung cancer mice, with faster growth in the metastasis, compared with the same lung cancer-prone bone metastasis, which did not differ significantly in the experiment immunological team of mice (left) and nicotine (right) showed high levels of activated small glial cells in the metastasis of the mice in the nicotine group, mostly M2, compared with a much lower type of M1 researchers injected the brains of mice with CSF1 receptor inhibitor PLX3397, which eliminated about 99% of small glial cells in the brain, and indeed the brain metastasis in lung cancer mice was significantly inhibited and the survival of the abrain metastasis significantly increased sequencing results showed that nicotine increased the expression of argininase 1, arginase 2 and CD204 genes, as well as the activity of the JAK/STAT3 signaling pathway, which are characteristics of small glial cells to M2 type polarization polarized M2 small glial cells inducean seismostiac tumor cells to induce an increase in THE expression of SOX2 and NANOG genes, which are important genes in stem cells and maintain the "dryness" of stem cells' high self-renewal and differentiation ability , M2 increases the secretion of insulin-like growth factor 1 (IGF1) and chemo-factor CCL20, one growth-promoting, one-boosting aggregation, and therefore, too much M2 leads to the rapid formation of brain metastasis not only, nicotine inhibits the ability to swallow small glial cells, while increasing the expression of CD47 on tumor cells CD47 is the "death-free gold medal" of tumor cells, which transmits a "don't eat me" signal to immune cells by mimicking normal cells, disguised as normal cells to evade immune cells , nicotine not only acts on small glial cells, inhibiting swallowing power, allowing them to activate in the direction of growth-promoting phenotypes, but also in tumor cells, helping them avoid immune cells based on these results, the researchers thought that avoiding the polarization of small glial cells toward M2 might be a potential treatment to block brain metastasis in lung cancer they screened a pool of natural compounds and found three of the 103 known compounds that could cross the blood-brain barrier, effectively inhibiting the activation of nicotine-induced M2 small glial cell-related gene promoters at a low concentration of 1 sM the most inhibitive of which is the small chrysanthemum ester, promoter activity is reduced by more than 20 times is derived from a small white chrysanthemum and is used in Europe to treat inflammation and headaches and previous studies have found that it regulates signal conduction of the JAK/STAT3 signalpath this experiment also confirmed that the small chrysanthemum inhibits JAK/ STAT3 signal, reduces M2 type small glial cells, and restores the swallowing ability of small glial cells, mice have a double increase in the survival of cerebral metastatic survival! The mice's weight was not affected and liver toxicity was not checked changes in survival rates in the mice control group (green), nicotine (red), and nicotine-treated small chrysanthemum treatment group (black), researchers believe this may represent a new treatment for brain metastasis in lung cancer, especially in patients with smoking lung cancer most importantly, unlike chemotherapy drugs, it can cross the blood-brain barrier and is not highly toxic Dr Kounosuke Watabe, the study's communications author, said he hopes to work with clinical oncologists in the near future to test the effects of chrysanthemums in clinical trials to inhibit brain metastasis in lung cancer .