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Written | nagashi editor | Wang Cong layout | Shui Chengwen Every human body has a special clock-the biological clock, which manages the circadian rhythm in our body.
It is worth noting that circadian rhythm disorders can have a negative impact on the body, which is manifested in proliferative, metabolic and immune diseases, posing a huge threat to global health.
Given that circadian rhythm disorders can cause fluctuations in the body's immune capacity, it is a very important study to explore whether circadian rhythm disorders can inhibit tumor-related immune cells and ultimately promote tumor tissue growth.
In October 2020, researchers from the University of Buenos Aires in Argentina and Virginia Tech published a research paper titled: Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation in the Science Advances journal.
This study shows that in a mouse melanoma model, compared with the normal light-dark cycle (LD), the circadian rhythm disorder will lead to the loss or reversal of the levels of macrophages and cytokines in the liver and tumor tissues of the mice.
, And increase the tumor growth rate and reduce the incubation period.
The biological clock mainly exists in the suprachiasmatic nucleus (SCN) of the hypothalamus, and the main environmental signal regulating its activity is the light-dark cycle (LD).
In turn, SCN can control the circadian rhythm of peripheral tissues (such as liver, lung and other brain regions) through nerve, hormone and behavioral pathways to maintain the best phase relationship between them and the environment.
In mammals, long-term circadian rhythm disorders can lead to many diseases, such as cardiometabolic syndrome, obesity, and physical and mental health disorders.
At the same time, studies have shown that circadian rhythm imbalance can also affect the expression of related genes such as cell cycle, cell death and DNA damage, thereby increasing the growth rate of tumors.
In this study, the researchers explored the effect of interruption of circadian rhythm on tumor growth rate in a mouse model of non-metastatic melanoma.
They found that compared with the control group mice under normal conditions, the experimental group mice under the condition of circadian rhythm disorders, the tumor growth volume was significantly increased, and the difference in survival curves between the two groups was statistically significant (P = 0.
0153 ).
Characteristics of tumor growth and survival of experimental mice under circadian rhythms.
Next, the research team verified whether changes in light time affect the formation of tumor blood vessels.
By comparing the number of blood vessels at the site of tumor vascular cell inoculation in the two groups, they found that the number of blood vessels in the tumor increased significantly under the condition of interrupted circadian rhythm (P=0.
0007).
At the same time, because the composition of the tumor immune microenvironment can significantly affect the growth of tumors, the researchers explored whether circadian rhythm disorders can affect the proportion of various immune cells in the tumor microenvironment and ultimately promote tumor progression.
The research team first tested the proportions of different tumor-infiltrating white blood cells in the tumor samples of the two groups of mice.
They found that there was no significant difference in the percentage of total macrophages in the tumor samples, but M1 (pro-inflammatory) and M2 (pro-inflammatory) and M2 ( However, the level of anti-inflammatory macrophages has been significantly reduced.
The circadian rhythm disorder causes the level of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages in the experimental mice to decrease.
In this context, the circadian rhythm disorder also causes the liver rhythmic clock gene expression abnormalities and cell cycle in the mice.
Abnormal expression of cyclin genes, increased levels of CcnA2 in tumors, and decreased expression of cell cycle inhibitor p21WAF/CIP1, all of which will increase the rate of tumor proliferation. Under the condition of circadian rhythm disorders, liver clock gene expression is abnormal.
In general, this study shows that circadian rhythm disorders can promote tumor growth by regulating immune response and cell cycle regulators.
The author of the paper said that this is specifically manifested in the spleen and The percentage of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in tumors changes significantly under conditions of circadian imbalance, and the decrease in the ratio of M1/M2 macrophages will promote tumor escape and tumor progression.
Link to the paper: https://advances.
sciencemag.
org/content/6/42/eaaz4530 Open to reprint this article Open to reprint: just leave a message in this article to inform
It is worth noting that circadian rhythm disorders can have a negative impact on the body, which is manifested in proliferative, metabolic and immune diseases, posing a huge threat to global health.
Given that circadian rhythm disorders can cause fluctuations in the body's immune capacity, it is a very important study to explore whether circadian rhythm disorders can inhibit tumor-related immune cells and ultimately promote tumor tissue growth.
In October 2020, researchers from the University of Buenos Aires in Argentina and Virginia Tech published a research paper titled: Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation in the Science Advances journal.
This study shows that in a mouse melanoma model, compared with the normal light-dark cycle (LD), the circadian rhythm disorder will lead to the loss or reversal of the levels of macrophages and cytokines in the liver and tumor tissues of the mice.
, And increase the tumor growth rate and reduce the incubation period.
The biological clock mainly exists in the suprachiasmatic nucleus (SCN) of the hypothalamus, and the main environmental signal regulating its activity is the light-dark cycle (LD).
In turn, SCN can control the circadian rhythm of peripheral tissues (such as liver, lung and other brain regions) through nerve, hormone and behavioral pathways to maintain the best phase relationship between them and the environment.
In mammals, long-term circadian rhythm disorders can lead to many diseases, such as cardiometabolic syndrome, obesity, and physical and mental health disorders.
At the same time, studies have shown that circadian rhythm imbalance can also affect the expression of related genes such as cell cycle, cell death and DNA damage, thereby increasing the growth rate of tumors.
In this study, the researchers explored the effect of interruption of circadian rhythm on tumor growth rate in a mouse model of non-metastatic melanoma.
They found that compared with the control group mice under normal conditions, the experimental group mice under the condition of circadian rhythm disorders, the tumor growth volume was significantly increased, and the difference in survival curves between the two groups was statistically significant (P = 0.
0153 ).
Characteristics of tumor growth and survival of experimental mice under circadian rhythms.
Next, the research team verified whether changes in light time affect the formation of tumor blood vessels.
By comparing the number of blood vessels at the site of tumor vascular cell inoculation in the two groups, they found that the number of blood vessels in the tumor increased significantly under the condition of interrupted circadian rhythm (P=0.
0007).
At the same time, because the composition of the tumor immune microenvironment can significantly affect the growth of tumors, the researchers explored whether circadian rhythm disorders can affect the proportion of various immune cells in the tumor microenvironment and ultimately promote tumor progression.
The research team first tested the proportions of different tumor-infiltrating white blood cells in the tumor samples of the two groups of mice.
They found that there was no significant difference in the percentage of total macrophages in the tumor samples, but M1 (pro-inflammatory) and M2 (pro-inflammatory) and M2 ( However, the level of anti-inflammatory macrophages has been significantly reduced.
The circadian rhythm disorder causes the level of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages in the experimental mice to decrease.
In this context, the circadian rhythm disorder also causes the liver rhythmic clock gene expression abnormalities and cell cycle in the mice.
Abnormal expression of cyclin genes, increased levels of CcnA2 in tumors, and decreased expression of cell cycle inhibitor p21WAF/CIP1, all of which will increase the rate of tumor proliferation. Under the condition of circadian rhythm disorders, liver clock gene expression is abnormal.
In general, this study shows that circadian rhythm disorders can promote tumor growth by regulating immune response and cell cycle regulators.
The author of the paper said that this is specifically manifested in the spleen and The percentage of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in tumors changes significantly under conditions of circadian imbalance, and the decrease in the ratio of M1/M2 macrophages will promote tumor escape and tumor progression.
Link to the paper: https://advances.
sciencemag.
org/content/6/42/eaaz4530 Open to reprint this article Open to reprint: just leave a message in this article to inform
