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Background Altering the systemic milieu through exercise has been proposed as a potential mechanism underlying exercise-driven tumour suppression. It is not yet known whether men with advanced prostate cancer can elicit such adaptations following a program of exercise. The purpose is to examine myokine levels of serum acquired from metastatic castrate-resistant prostate cancer (mCRPC) patients recruited to the INTERVAL-GAP4 trial before and after 6 months of exercise and its tumour-suppressive effect. Methods Twenty-five men with mCRPC (age = 74.7 ± 7.1 yrs) were randomised to supervised multimodal (aerobic and resistance) exercise (EX) or self-directed exercise control group (CON). Body composition was assessed using dual-energy x-ray absorptiometry (DXA), and fasting blood in a rested state was collected at baseline and at 6 months. Serum levels of myokines (SPARC, OSM, decorin, IGF-1, and IGFBP-3) were measured. Serum was applied to the prostate cancer cell line DU145, and growth was assessed for 72 h. Results No significant change in body composition was observed. Adjusted serum OSM (P = 0.050) and relative OSM (P = 0.083), serum SPARC (P = 0.022) and relative SPARC (P = 0.025) increased in EX compared to CON. The area under curve (AUC) over 72 h showed a significant reduction in DU145 growth after applying post-intervention serum from the EX vs CON (P = 0.029). Conclusion Elevated myokine expressions and greater tumour-suppressive effects of serum after 6 months of periodised and autoregulated supervised exercise was observed in men with mCRPC. Exercise-induced systemic changes may slow disease progression in men with advanced prostate cancer.

Although several mechanisms have been proposed for the tumor-suppressive effect of exercise, little attention has been given to myokines, even though skeletal muscle is heavily recruited during exercise resulting in myokine surges. We measured resting serum myokine levels before and after an exercise-based intervention and the effect of this serum on prostate cancer cell growth. Methods: Ten prostate cancer patients undertaking androgen deprivation therapy (age, 73.3 ± 5.6 yr) undertook a 12-wk exercise-based intervention including supervised resistance training, self-directed aerobic exercise, and protein supplementation. Body composition was assessed by dual-energy x-ray absorptiometry and muscle strength by the one-repetition maximum method. Fasting blood was collected at baseline and postintervention, and serum levels of myokines -secreted protein acidic and rich in cysteine, oncostatin M (OSM), decorin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 (IGFBP-3)-were measured. The growth of the prostate cancer cell line DU145 with baseline and postintervention serum was measured. Results: Body weight ( P = 0.011), fat mass ( P = 0.012), and percent body fat ( P = 0.033) were reduced, whereas percent lean mass ( P = 0.001) increased, as did strength (leg press, P = 0.006; chest press, P = 0.020) across the intervention. Serum OSM levels ( P = 0.020) and relative serum OSM levels ( P = 0.020) increased compared with baseline. A significant reduction in DU145 Cell Index ( P = 0.012) and growth rate ( P = 0.012) was observed after applying postintervention serum compared with baseline serum. Conclusions: This study provides evidence for enhanced myokine expression and tumor-suppressive effects of serum from chronically exercise-trained prostate cancer patients on androgen deprivation therapy.

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Physical exercise is increasingly recognized as a valuable treatment strategy in managing prostate cancer, not only enhancing supportive care but potentially influencing disease outcomes. However, there are limited studies investigating mechanisms of the tumor-suppressive effect of exercise. Recently, extracellular vesicles (EVs) have been recognized as a therapeutic target for cancer as tumor-derived EVs have the potential to promote metastatic capacity by transferring oncogenic proteins, integrins, and microRNAs to other cells and EVs are also involved in developing drug resistance. Skeletal muscle has been identified as an endocrine organ, releasing EVs into the circulation, and levels of EV-containing factors have been shown to increase in response to exercise. Moreover, preclinical studies have demonstrated the tumor-suppressive effect of protein and microRNA contents in skeletal muscle-derived EVs in various cancers, including prostate cancer. Here we review current knowledge of the tumor-derived EVs in prostate cancer progression and metastasis, the role of exercise in skeletal muscle-derived EVs circulating levels and the alteration of their contents, and the potential tumor-suppressive effect of skeletal muscle-derived EV contents in prostate cancer. In addition, we review the proposed mechanism of exercise in the uptake of skeletal muscle-derived EVs in prostate cancer.

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In the original version of the article, the name of author Elin Gray was misspelled as Elin Grey. The author's name has now been updated to the correct spelling in the HTML and PDF versions of the article.

A prominent toxicity of androgen suppression in patients with prostate cancer (PCa) is loss of skeletal muscle. Exercise may induce tumor suppression through the endocrinal function of skeletal muscle; however, this is currently unknown. In this review, we summarize our work demonstrating the acute and chronic myokine response to exercise and the tumor-suppressive effect of circulatory milieu alteration in PCa patients. Key Words: exercise medicine, myokines, skeletal muscle, prostate cancer, androgen suppression KEY POINTS• Androgen suppression causes a substantial decline of skeletal muscle mass due to loss of the androgen-activated anabolic signal. • Despite skeletal muscle deficiencies in patients, circulatory levels of myokines are altered by acute and chronic exercise. • In the presence of serum collected from patients undertaking androgen suppression, prostate cancer cell growth was reduced after acute and chronic exercise. • A bout of exercise may provide additional tumor suppression to the anticancer environment established by regular exercise. • This specific mechanism may explain reduced disease progression and increased survival in patients with prostate cancer who are more physically active.