International Business Department           Liu Bojia           Feburary 28, 2023

  Stress is an inevitable part of life, and in moderation, we are able to deal with it and burn it off on our own, returning to normal life. But too much stress, or prolonged exposure to stress, can have many negative effects, and several studies have linked high stress levels to an increased risk of a variety of diseases, including depression, Alzheimer's disease, and cardiovascular disease.

  And in the recent journal Cancer Cell, scientists from Cold Spring Harbor Laboratory have added another hazard of stress - promoting the spread of cancer cells. The study found that long-term chronic stress accelerates the formation of a special meshwork of neutrophils, which can help cancer cells metastasise.

  The paper points out that the stress of cancer patients cannot be ignored; even after accepting the onset of the disease, patients continue to worry about the progression of the cancer and the response to various treatments, and this chronic stress affects a wide range of physiological processes internally.

  Some past experiments in oncology animals have shown that chronic stress stimuli can promote primary tumour growth, while these animals are more likely to develop cancer metastases. In the new study, the authors selected a mouse model of breast cancer to observe, and they exposed some of the mice to moderate and continuous stress stimuli on a daily basis. The results showed that chronic stress doubled the size of the tumours in the mice and increased the occurrence of metastases by two to four times.

  Meanwhile, the immune status in the in situ tumours was not encouraging, with analysis showing that the tumours were infiltrated with fewer T cells and more neutrophils. Despite the importance of neutrophils in fighting pathogenic infections, their presence in large numbers in tumours is not a good thing, and excessively high levels of neutrophils tend to be associated with a worse prognosis in cancer.

  The reason for this is the special structure that neutrophils form - the neutrophil extracellular trap (NET), which is a DNA network structure containing neutrophil proteins. This network traps pathogens and also remodels the peripheral environment of the tumour, serving as a base for metastasis and invasion.

  And the research confirms that glucocorticoids are elevated in the body under chronic stress, and this stress hormone can act on neutrophils, and at the same time make the neutrophils change their characteristics, such as changing the peak time of cellular activity and increasing the production of reactive oxygen species by the cells, which has a contributing effect on the formation of NETs.

  The authors extracted some neutrophils from the blood of tumour-bearing mice under chronic stress, and as a result, these cells were able to form more NETs in vitro than the control group, which also suggests that stress confers a stronger NET-forming ability on neutrophils.

  Based on these results, the researchers found that there are 3 ways to reduce tumour metastasis, the first is to remove neutrophils through antibody therapy; the second is to inhibit NET formation with drugs; and the third is to make neutrophils lose their response to glucocorticoids. All of these approaches significantly reduced the occurrence of metastases in tumour-bearing mice.

  In addition to tumour-bearing mice, healthy mice also developed more NETs in their lungs under long-term chronic stress, which alters the structure of healthy lung tissue. The authors suggest that this may set the stage for cancer development. And reducing stress to prevent NET formation could be a potential strategy to reduce the risk of tumour metastasis in the future.