EFFECT OF EXERCISE-CONDITIONED SERA FROM CHILDREN WITH CANCER ON THE PROLIFERATION OF EWING SARCOMA AND RHABDOMYOSARCOMA CELLS

INTRODUCTION: Exercise not only improves the fitness and well-being of adult cancer patients, but it also has direct effects on cancer itself including effects on cancer cell proliferation. Childhood cancers differ from adult cancers, and it is poorly understood whether exercise affects cancer hallmarks in pediatric cancer patients. The aim of this study was therefore to 1) investigate whether incubation of two sarcoma cell lines with exercise-conditioned sera alters cell proliferation compared to resting sera and 2) whether there are metabolite biomarkers whose concentration predicts the proliferative/mitotic effect of a serum. METHODS: We screened 212 patients with pediatric malignancies of which 11 children performed a high intensity interval training (HIIT) with 10 x 15 s intervals (1). Blood was drawn before and after the exercise and processed to serum. Subsequently, we incubated Ewing sarcoma (A673) and rhabdomyosarcoma (RD) cells with 10% exercise-conditioned or control media in triplicates and measured cell proliferation by WST-1 assay. Proliferation data were further correlated to serum metabolites quantified by mass spectrometry (AbsoluteIDQ p180 kit). RESULTS: To find out whether exercise alters A673 and RD proliferation, we incubated these cells with the resting and exercise-conditioned sera and measured proliferation by WST-1 assay. When compared to sera taken at rest, exerciseconditioned sera reduced proliferation of A673 cells by 7 ± 30% (p=0.2), and of RD cells by 3 ± 7% (p=0.22), respectively. However, the inter-individual difference between proliferation responses to patient sera was greater: up to 400% for the A673 cell line and 84% for the RD cell line. Next, to identify possible metabolite biomarkers for proliferation, we correlated exercise-induced metabolite concentration changes with exercise-induced proliferation changes. This revealed two metabolite concentration ratios: Ornithine (Orn) to Arginine (Arg) (RD cells: r=0.788, p=0.006; A673 cells: r=0.782, p=0.006) and Asymmetric Dimethylarginine (ADMA) to Arg (RD cells: r=0.910, p=0.0002; A673 cells: r= 0.622, p=0.045). CONCLUSION: The main finding of this study is that exercise-conditioned sera decreased the proliferation of Ewing sarcoma and rhabdomyosarcoma cells by less than 10%. However, we found large inter-individual variations in the proliferation effect of sera from different patients. Moreover, the serum changes of the ADMA/Arg and Orn/Arg ratios in response to exercise correlate with the change of proliferation in sarcoma cells, identifying ADMA/Arg and Orn/Arg ratios as candidate biomarkers for the proliferation effect of sera. 1) S. Kesting, et al. Cancers, 14(6), 2022     «

INTRODUCTION: Exercise not only improves the fitness and well-being of adult cancer patients, but it also has direct effects on cancer itself including effects on cancer cell proliferation. Childhood cancers differ from adult cancers, and it is poorly understood whether exercise affects cancer hallmarks in pediatric cancer patients. The aim of this study was therefore to 1) investigate whether incubation of two sarcoma cell lines with exercise-conditioned sera alters cell proliferation compared...     »