Current DateSeptember 17, 2021

Stress awakens dormant tumor cells

Successful cancer treatment does not always mean a lasting cure. Stress hormones and immune cells can help reactivate dormant tumor cells so that they re-form cancerous ulcers. As researchers have shown in mice, stress hormones cause certain white blood cells to increasingly release proteins that lead to the re-division of tumor cells. Data from 80 former lung cancer patients also show that people with high levels of these proteins are more likely to experience relapses. Treatment with beta-blockers could help, which reduces stress reactions in the body.

The renewed growth of tumors is one of the most common causes of death for cancer patients. Often these so-called recurrences occur years after a successful operation or chemotherapy. This is due to inactive tumor cells, which remain in a kind of resting state in the body after therapy. Since chemotherapy almost always targets sharing cells, these dormant cells escape treatment. The mechanisms for how and why dormant tumor cells become active again are the subject of current research. Inflammation processes, which are mediated by immune cells, are suspected to play a role in this.

Cancer return in stressed mice

A team led by Michela Perego of the Wistar Institute in Philadelphia has now investigated how stress-related immune responses affect tumor growth. To do this, they first made sure that they developed lung cancer in mice. After surgical removal of the tumor and chemotherapy, they exposed some of the mice daily to stressful situations and observed in which animals relapsed. The result: After three weeks, tumors had grown again in all stressed mice. Of the unstressed animals, on the other hand, none had developed a tumor again.

Blood samples from the mice showed that the stressed animals had significantly increased levels of two proteins, S100A8 and S100A9, which are released by certain immune cells called neutrophils in response to stress. These proteins, together with fat molecules they modified, ensured that the dormant cancer cells became active again. On the one hand, the researchers demonstrated this in cell cultures. On the other hand, they also used six mice that could not produce the proteins S100A8 and S100A9. In fact, despite stress, only one of these mice developed a tumor recurrence.

Beta blockers as a prevention?

Analysis of data from 80 patients who had undergone lung cancer treatment also showed that S100A8 and S100A9 could play an important role in the tumor’s return. In 11 out of 35 patients who had high levels of these two proteins in their blood, recurrence occurred within 33 months (31.4 percent). By contrast, out of 45 patients with low levels of proteins, only six had a recurrence (13.3 percent) during this time.

Perego and colleagues explored a possible preventive measure on the mouse model. To reduce the stress response, they treated part of the mice with a beta-blocker that mitigates the effect of stress hormones. In fact, despite stress, the animals treated in this way had significantly lower levels of S100A8 and S100A9 and were less likely to re-form tumors. “This fits with clinical observations that lung cancer patients who take beta-blockers survive longer,” the researchers write. There is already evidence that such drugs improve survival chances for breast cancer, ovarian cancer, pancreatic cancer and skin cancer.

“Our results provide insight into the mechanisms involved in reactivating dormant tumor cells,” the researchers conclude. “In doing so, they point to possible therapeutic strategies for delaying or preventing the recurrence of tumours.” If these results are confirmed in further studies, they could potentially contribute to the follow-up treatment of cancer patients in the future.

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