Noradrenaline has Different Effects on Rhabdomyosarcoma and Ewing’s Sarcoma Cancer Hallmarks – Implications for Exercise Oncology

Background: Exercise has beneficial effects on cancer and its treatment, but the underlying mechanisms are poorly understood. Some studies have linked the positive impact of exercise to catecholamine signaling. In contrast, cancer stress studies typically report that catecholamines worsen cancer hallmarks and outcomes. Here, we aimed to investigate whether adrenergic receptor isoform expression can explain the contradictory effects of catecholamines in cancer. Methods: We cultured two pediatric sarcoma cancer cell lines that either express (A673 cell line) or do not express (RD cell line) adrenergic receptors. Cells were treated with a 5x dilution series of noradrenaline to assess the effect of noradrenaline on cell numbers. After these dose-finding experiments, we treated both cancer cell lines with 60 μM noradrenaline to examine the effect of noradrenaline on cell proliferation, migration, and cAMP signaling. Results: Treatment with 60 μM noradrenaline significantly decreased cell numbers by 61.89 ± 10.36 (p ≤ 0.001), decreased cell proliferation by 15.88% ± 6.76 (p ≤ 0.05), decreased cell migration after 24 hours (p ≤ 0.001), and increased cAMP concentrations 38-fold (p ≤ 0.001) in A673 cells that express adrenergic receptors, but not in RD cells that do not express adrenergic receptors. Conclusion: Our results indicate as a proof of principle that the effect of catecholamines on cancer progression and metastasis might depend on the expression of the nine adrenergic receptor isoforms. As cancers express adrenergic and other receptors differentially, this has implications for the response of cancers to exercise, stress and medication and may help to further personalize cancer treatments.     «

Background: Exercise has beneficial effects on cancer and its treatment, but the underlying mechanisms are poorly understood. Some studies have linked the positive impact of exercise to catecholamine signaling. In contrast, cancer stress studies typically report that catecholamines worsen cancer hallmarks and outcomes. Here, we aimed to investigate whether adrenergic receptor isoform expression can explain the contradictory effects of catecholamines in cancer. Methods: We cultured two pediatric...     »