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oai:docta.ucm.es:20.500.14352/1214732025-06-18T23:48:42Zcom_20.500.14352_14col_20.500.14352_15

Exercise and tumor proteome: insights from a neuroblastoma model González Gálvez, Beatriz Martín Ruiz Valdepeñas, María Asunción Plaza-Florido, Abel López, Juan A. Santos-Lozano, Alejandro Zazo, Sandra Rincón-Castanedo, Cecilia Lumbreras, Jorge Terrón-Camero, Laura C. López-Soto, Alejandro Andrés-León, Eduardo González-Murillo, África Rojo, Federico Ramírez, Manuel Lucía, Alejandro Fluza-Luces, Carmen 616.851.7 612.014 616-006 Ciencias Biomédicas Oncología Fisiología 32 Ciencias Médicas 3201.01 Oncología 2410 Biología Humana 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) 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. National Institutes of Health Wereld Kanker Onderzoek Fonds (WKOF) Ministerio de Ciencia e Innovación (España) European Commission Instituto de Salud Carlos III Ministerio de Ciencia, Innovación y Universidades (España) Fundación Pro CNIC Depto. de Bioquímica y Biología Molecular Fac. de Farmacia TRUE pub 2025-06-18T08:53:12Z 2025-06-18T08:53:12Z 2024 journal article VoR https://hdl.handle.net/20.500.14352/121473 XXXX-XXXX 10.1152/physiolgenomics.00064.2024 eng info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00139/ES/EJERCICIO COMO TERAPIA COADYUVANTE EN CANCER PEDIATRICO (TUMORES SOLIDOS): DEL LABORATORIO A LA CLINICA. PARTE 1: EJERCICIO EN NEUROBLASTOMA (ESTUDIO PRECLINICO Y CLINICO)./ info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00645/ES/EJERCICIO FISICO Y ASESORAMIENTO EN SALUD PARA ADOLESCENTES CON CANCER: UNA VISION INTEGRADORA./ info:eu-repo/grantAgreement/ISCIII//PI23/00396 info:eu-repo/grantAgreement/ISCIII//FORT23/00023 info:eu-repo/grantAgreement/AEI//CEX2020-001041-S 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. restricted access application/pdf American Physiological Society