Tumor Suppressor Pathway Activated by Exercise May Reduce Breast Cancer Risk

Moderate- to high-intensity exercise may lead to an acute increase in levels of epinephrine, which can reduce breast cancer cell viability and tumor growth via activation of the Hippo signaling pathway, according to researchers in Denmark. They report in the journal Cancer Research that serum obtained from women with breast cancer immediately after finishing 2 hours of moderate to intense exercise suggests that epinephrine activation of the Hippo signaling pathway helps prevent the growth and survival of breast cancer cell lines in vitro and in mice.

“I’m surprised how strong the effect of exercise and epinephrine was on tumor formation and metastasis. Only half of the mice developed small tumors in the ones injected with hormone sensitive breast cancer cells, after these cells had been incubated with patient serum taken immediately after an exercise training session. This effect was lost if we blocked adrenergic signaling,” said study investigator Pernille Hojman, PhD, from the Centre of Inflammation and Metabolism at Copenhagen University Hospital, Copenhagen, Denmark.

It has been known for decades that there is a strong protective effect of physical activity on breast cancer risk, recurrence, and mortality. However, the underlying mechanisms have not been fully understood. Hojman and colleagues used human exercise–conditioned serum for breast cancer cell incubation studies and murine exercise interventions to try to identify exercise factors and signaling pathways involved in the exercise-dependent suppression of breast cancer.

The team obtained blood samples before and after 2 hours of moderate to intense exercise from 7 healthy women and 20 women who were being treated with adjuvant chemotherapy after surgery for early-stage breast cancer. Serum obtained after exercise from both healthy women and those with breast cancer reduced the survival of two breast cancer cell lines, MCF-7 and MDA-MB-231, in vitro compared with serum obtained before exercise. It also significantly reduced the ability of MCF-7 cells to form tumors if injected into mice. The study showed that 45 % of mice receiving the cells exposed to serum obtained after exercise developed tumors compared with 90% of mice receiving cells exposed to serum obtained at rest.

“We are working with exercise interventions during the preoperative phase. We are planning to start a randomized controlled exercise intervention study in patients with upper gastrointestinal cancer during their 12 weeks of neoadjuvant chemotherapy. Here the aims are to study the effect of exercise training on risk of postoperative complications, as well as tumor specific regulation of the Hippo signaling,” Hojman told OncoTherapy Network.

Hojman said the important message is that exercise can have an effect on tumor cell growth and the metastasis process. Yet this regulation is dependent on increases in epinephrine. This can be obtained if the performed exercise is of moderate to high intensity and associated with increases in heart rate and heavy breathing.