Exercise and tumor proteome: Insights from a neuroblastoma model

Abstract

Background/Aim: The impact of exercise on pediatric tumor biology is essentially unknown. We investigated the effects of regular exercise on tumor proteome profile (as assessed with liquid chromatography with tandem mass spectrometry) in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma (HR-NB). Methods: Tumor samples of 14 male mice (aged 6-8 weeks) that were randomly allocated into an exercise (5-week combined aerobic and resistance training) or nonexercise control group (6 and 8 mice per group, respectively) were analyzed. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to generate a protein-protein interaction (PPI) network and enrichment analyses. The Systems Biology Triangle (SBT) algorithm was applied for analyses at the functional category level. Results: Tumors of exercised mice showed a higher and lower abundance of 101 and 150 proteins, respectively, compared to controls [false discovery rate (FDR)<0.05], which were enriched in metabolic pathways, aminoacid metabolism, regulation of hormone levels, and peroxisome proliferator-activated receptor signaling pathway (FDR<0.05). The SBT algorithm indicated that 184 and 126 categories showed a lower and higher abundance, respectively, in the tumors of exercised mice (FDR<0.01). Categories with lower abundance were involved in energy production while those with higher abundance were related to transcription/translation, apoptosis, and tumor suppression. Conclusion: Regular exercise altered the abundance of hundreds of intratumoral proteins and molecular pathways, particularly those involved in energy metabolism, apoptosis, and tumor suppression. These findings provide preliminary evidence of the molecular mechanisms underlying potential effects of exercise in HR-NB.