Liz Meszaros, MDLinx | September 19, 2017
After moderate to intense exercise, epinephrine activation of the Hippo signaling pathway may work to prevent the growth and survival of breast cancer cell lines, as evidenced in vitro and in mice, according to results from a study published in the journal Cancer Research.
Although recent epidemiologic studies have indicated that exercise may lower the risk of recurrence in women with breast cancer, the molecular mechanisms behind this effect are unknown. Researchers led by Pernille Hojman, PhD, group leader in the Centre for Physical Activity Research at Copenhagen University Hospital, Denmark, conducted this study to determine whether training interventions that specifically target, molecularly, tumor progression, and metastasis can be designed.
Previously, Dr. Hojman and fellow researchers demonstrated that 2 hours of moderate to intense exercise by survivors of breast cancer can increase the level of a number of serum factors that work to reduce the survival of breast cancer cell lines in vitro. In this study, they sought to determine which factor was responsible for the effects on cell viability and the mechanisms behind it.
They obtained blood samples from 20 women being treated with adjuvant chemotherapy after surgery for early-stage breast cancer and 7 healthy controls, both before and after 2 hours of moderate to intense exercise. Subjects with breast cancer participated in a 6-week standard exercise rehabilitation program at the Copenhagen University Hospital.
Dr. Hojman and colleagues found that the 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. In addition, when injected into mice, the serum obtained after exercise also significantly reduced the ability of the MCF-7 cells to form tumors, with only 45% of mice injected with after-exercise serum developing tumors, compared with 90% of those that received serum obtained at rest.
Furthermore, they found that if epinephrine was blocked from its receptor on the surface of the MCF-7 cells, the effects of after-exercise serum on MCF-7 cell survival and the ability to form tumors in mice was significantly reduced. This effect was not seen, however, on MDA-MB-231 cells.
Upon further analysis, these researchers found that epinephrine in after-exercise serum activated the Hippo signaling pathway, a known tumor suppressor signaling pathway, in MCF-7 cells, but not MDA-MB-231 cells.
“The results of this study show that moderate to high intensity exercise leads 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,” said Dr. Hojman. “Although these data suggest that it might be optimal for women with breast cancer to exercise at a moderate to high intensity, further studies are needed to confirm this. Women who have been diagnosed with breast cancer should consult a doctor before embarking on an exercise program.”
She added: “MCF-7 cells are hormone receptor–positive and MDA-MB-231 cells are triple-negative. There are epidemiological data that suggest that exercise might be better at reducing the risk of recurrence of hormone receptor–positive breast cancer compared with triple-negative breast cancer, which might explain why the effects of serum obtained after exercise were more pronounced on MCF-7 cells. In addition, these cell lines differ in which mutations they carry, and the difference in the exercise effect might be a result of this.”
This study was supported by funds from the Danish Cancer Society, the Danish Cancer Research Foundation, the Dagmar Marshall’s Fund; the Centre of Physical Activity Research is supported by funds from TrygFonden.