Muscle‐derived cytokines reduce growth, viability and migratory activity of pancreatic cancer cells

The evidence that regular physical exercise reduces the risk of developing cancer is well described. However, the interaction between physical exercise and cancer is not fully clarified yet. Several myokines released by skeletal muscle appear to have a direct anti‐tumour function. There are few data on myokine secretion after exercise in patients with advanced tumours. Pancreatic cancer (PC) is a very aggressive and usually fatal cancer. To investigate the effects of exercise in PC, the blood of advanced‐stage PC patients was analysed after 12 weeks of resistance training using whole‐body electromyostimulation. After the 12‐week training period, the patient serum inhibited the proliferation and the motility of PC cells and enhanced PC cell apoptosis. The impact of exercise training was also investigated in an exercise‐mimicking in vitro model using electric pulse stimulation of human myotubes and revealed similar anti‐tumour effects on PC cells, clearly indicating direct cancer‐protective properties of activated skeletal muscle. Protein and gene expression analyses in plasma from exercise‐trained patients and in myotube cultures after in vitro exercise showed that interleukin 10 (IL10), C‐X‐C motif ligand 1 (CXCL1) and C‐C motif chemokine ligand 4 (CCL4) are myokines released from activated skeletal muscle. In accordance with the effects of serum from exercise‐trained patients, the supplementation with recombinant IL10, CXCL1 and CCL4 impaired growth and migration of PC cells. Treatment of PC cells with these myokines upregulated caspase 3/7 expression and the cleavage of poly(ADP‐ribose) polymerase, leading to enhanced PC cell death. The identification of myokines with anti‐tumour properties in advanced‐stage PC patients after exercise opens a new perspective in supportive therapy with sports and exercise for cancer patients.