Successful cancer treatment doesn’t always mean a permanent cure. Stress hormones and immune cells can help reactivate dormant tumor cells so that they can re-form canker sores. As researchers have shown in mice, stress hormones ensure that certain white blood cells secrete more proteins that cause the tumor cells to divide again. Data from 80 former lung cancer patients also show that people with high levels of these proteins are more likely to relapse. Treatment with beta blockers, which reduce stress reactions in the body, could possibly help.
Tumor regrowth is one of the leading causes of death in cancer patients. These so-called recurrences often occur years after a successful operation or chemotherapy. The cause of this are inactive tumor cells that remain in the body in a kind of resting state after therapy. Because chemotherapies almost always target dividing cells, these dormant cells escape treatment. The mechanisms of how and why dormant tumor cells become active again are the subject of current research. Inflammatory processes mediated by immune cells presumably play a role in this.
Cancer return in stressed mice
A team led by Michela Perego from the Wistar Institute in Philadelphia has now investigated how stress-related immune reactions affect tumor growth. To do this, they first ensured that mice developed lung cancer. After surgical removal of the tumor and chemotherapy, they exposed some of the mice to stressful situations every day and observed which animals relapsed. The result: After three weeks, tumors had grown again in all the stressed mice. In contrast, none of the non-stressed animals 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. Together with fat molecules modified by them, these proteins ensured that the dormant cancer cells became active again. The researchers demonstrated this on the one hand with cell cultures. On the other hand, they also used six mice that could not produce the proteins S100A8 and S100A9. And indeed: of these mice, only one developed a tumor recurrence despite the stress.
Beta blockers as prevention?
The analysis of the data from 80 patients who had undergone lung cancer treatment also showed that S100A8 and S100A9 could play an important role in the recurrence of the tumor. 11 of 35 patients who had high levels of these two proteins in their blood had recurrences within 33 months (31.4 percent). Of 45 patients with low protein levels, however, only six had a relapse within this time (13.3 percent).
Perego and colleagues used the mouse model to research a possible preventive measure. To reduce the stress reaction, they treated some of the mice with a beta blocker, which attenuates the effects of stress hormones. In fact, despite the stress, the animals treated in this way had significantly lower levels of S100A8 and S100A9 and less frequently re-tumors. “This fits in with clinical observations that lung cancer patients who take beta blockers survive longer,” the researchers write. For breast cancer, ovarian cancer, pancreatic cancer and skin cancer, there is already evidence that such drugs improve the chances of survival.
“Our results provide an insight into which mechanisms are involved in reactivating dormant tumor cells,” summarize the researchers. “They thus indicate possible therapeutic strategies for delaying or preventing the recurrence of tumors.” If these results are confirmed in further studies, they could possibly make a contribution to the follow-up treatment of cancer patients in the future.
Source: Michela Perego (Wistar Institute, Philadelphia) et al., Science Translational Medicine, doi: 10.1126 / scitranslmed.abb5817