RT Journal Article T1 Exercise and tumor proteome: insights from a neuroblastoma model A1 González Gálvez, Beatriz A1 Martín Ruiz Valdepeñas, María Asunción A1 Plaza-Florido, Abel A1 López, Juan A. A1 Santos-Lozano, Alejandro A1 Zazo, Sandra A1 Rincón-Castanedo, Cecilia A1 Lumbreras, Jorge A1 Terrón-Camero, Laura C. A1 López-Soto, Alejandro A1 Andrés-León, Eduardo A1 González-Murillo, África A1 Rojo, Federico A1 Ramírez, Manuel A1 Lucía, Alejandro A1 Fluza-Luces, Carmen AB The impact of exercise on pediatric tumor biology is essentially unknown. We explored 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). Tumor samples of 14 male mice (aged 6-8 wk) that were randomly allocated into an exercise (5-wk combined aerobic and resistance training) or nonexercise control group (6 and 8 mice/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. Tumors of exercised mice showed a higher and lower abundance of 101 and 150 proteins, respectively, than controls [false discovery rate (FDR) < 0.05]. These proteins were enriched in metabolic pathways, amino acid metabolism, regulation of hormone levels, and peroxisome proliferator-activated receptor signaling (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, whereas those with higher abundance were related to transcription/translation, apoptosis, and tumor suppression. 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 the potential effects of exercise in HR-NB. NEW & NOTEWORTHY We used liquid chromatography with tandem mass spectrometry to explore the impact of a 5-wk exercise intervention on the tumor proteome profile in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma. Exercise altered the abundance of hundreds of proteins and pathways, particularly those involved in energy metabolism and tumor suppression. These molecular changes could mediate, at least partly, the potential antitumorigenic effects of exercise. PB American Physiological Society YR 2024 FD 2024 LK https://hdl.handle.net/20.500.14352/121473 UL https://hdl.handle.net/20.500.14352/121473 LA eng NO Plaza-Florido A, Gálvez BG, López JA, Santos-Lozano A, Zazo S, Rincón-Castanedo C, et al. Exercise and tumor proteome: insights from a neuroblastoma model. Physiological Genomics 2024;56:833–44. https://doi.org/10.1152/physiolgenomics.00064.2024. NO A.P.-F. is supported in part by National Institutes of Health Grant U01TR002004 (REACH project). Research by A.L. and C.F.- L. is funded by the Wereld Kanker Onderzoek Fonds (WKOF) as part of the World Cancer Research Fund International grant program (Grant IIG_FULL_2021_007) and the Spanish Ministry of Science and Innovation [Fondo de Investigaciones Sanitarias (FIS)] and Fondos FEDER (Grant PI18/00139). Research by C.F.-L. is funded by the Spanish Ministry of Science and Innovation [Fondo de Investigaciones Sanitarias (FIS)] and Fondos FEDER (Grants PI20/00645, PI23/00396, and FORT23/00023), by the Ministerio de Ciencia e Innovacion (Grant CNS2023-144144), and by a Miguel Servet postdoctoral contract granted by Instituto de Salud Carlos III (CP18/00034). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovacion Y Universidades (MICIU) and the Pro CNIC Foundation, and the Severo Ochoa Center of Excellence (Grant CEX2020- 001041-S funded by MICIU/AEI/10.13039/501100011033) NO National Institutes of Health NO Wereld Kanker Onderzoek Fonds (WKOF) NO Ministerio de Ciencia e Innovación (España) NO European Commission NO Instituto de Salud Carlos III NO Ministerio de Ciencia, Innovación y Universidades (España) NO Fundación Pro CNIC DS Docta Complutense RD 22 ene 2026