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Tumor Signatures of Physical Fitness : Insights from a Preclinical Model

Santos-Lozano, Alejandro ; Plaza-Florido, Abel ; Carrera-Bastos, Pedro LU ; Pérez-Prieto, Inmaculada ; Hernández-Belmonte, Alejandro ; Kamalinejad, Fatemeh ; Gálvez, Beatriz G. ; López, Juan A. ; Lumbreras, Jorge and Rincón-Castanedo, Cecilia , et al. (2025) In Medicine and Science in Sports and Exercise
Abstract

Purpose: Cardiorespiratory fitness (CRF) and muscle strength are associated with cancer risk/mortality in adults. However, there is yet no evidence for pediatric tumors. This study investigated the association of CRF and muscle strength with several tumor-related phenotypes in an aggressive childhood malignancy, high-risk neuroblastoma (HR-NB). Methods: Twelve mice bearing orthotopic HR-NB were studied. CRF and muscle strength were assessed using treadmill and grip strength testing, respectively. The following tumor-related outcomes were studied: survival, clinical severity, tumor weight/volume, metastasis, and intratumor immune infiltrates. Additionally, tumor samples underwent quantitative proteomic analysis via liquid... (More)

Purpose: Cardiorespiratory fitness (CRF) and muscle strength are associated with cancer risk/mortality in adults. However, there is yet no evidence for pediatric tumors. This study investigated the association of CRF and muscle strength with several tumor-related phenotypes in an aggressive childhood malignancy, high-risk neuroblastoma (HR-NB). Methods: Twelve mice bearing orthotopic HR-NB were studied. CRF and muscle strength were assessed using treadmill and grip strength testing, respectively. The following tumor-related outcomes were studied: survival, clinical severity, tumor weight/volume, metastasis, and intratumor immune infiltrates. Additionally, tumor samples underwent quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry. Spearman correlations (or logistic regression) were performed between CRF/muscle strength and the abovementioned variables. Proteins significantly correlated with CRF or muscle strength were mapped into protein–protein interaction (PPI) networks using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Results: CRF was inversely correlated with clinical severity score (r=–0.657, p=0.020). Of 6,840 identified tumor proteins, 76 correlated significantly with CRF (19 positively, 57 negatively), whereas 194 correlated with muscle strength (97 positively, 97 negatively). Proteins correlated with CRF were primarily involved in metabolic and structural pathways, including angiotensinogen and elastin. In turn, muscle strength-associated proteins were more abundant, and included keratin family proteins (e.g., keratin, type I cytoskeletal 14 and type II cytoskeletal 5), proteins involved in cell adhesion (e.g., desmoglein-1-alpha), and translational regulators (e.g., eukaryotic initiation factor 4A). Network analysis revealed significant enrichment in structural organization and cellular adhesion pathways. Conclusions: Besides the association of CRF with clinical severity of the tumor, distinct novel tumor proteomic signatures associated with CRF and muscle strength were identified, highlighting potential mechanisms linking physical fitness with childhood cancer biology.

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organization
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type
Contribution to journal
publication status
epub
subject
keywords
CANCER, CARDIORESPIRATORY FITNESS, EXERCISE, MUSCLE STRENGTH, ONCOLOGY, TUMOR BIOLOGY, TUMOR IMMUNE INFILTRATES
in
Medicine and Science in Sports and Exercise
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:105015075961
  • pmid:40857066
ISSN
0195-9131
DOI
10.1249/MSS.0000000000003836
language
English
LU publication?
yes
id
20189ebf-1b0c-479b-9d6c-d0c51ea92207
date added to LUP
2025-11-14 13:28:28
date last changed
2025-12-12 16:25:42
@article{20189ebf-1b0c-479b-9d6c-d0c51ea92207,
  abstract     = {{<p>Purpose: Cardiorespiratory fitness (CRF) and muscle strength are associated with cancer risk/mortality in adults. However, there is yet no evidence for pediatric tumors. This study investigated the association of CRF and muscle strength with several tumor-related phenotypes in an aggressive childhood malignancy, high-risk neuroblastoma (HR-NB). Methods: Twelve mice bearing orthotopic HR-NB were studied. CRF and muscle strength were assessed using treadmill and grip strength testing, respectively. The following tumor-related outcomes were studied: survival, clinical severity, tumor weight/volume, metastasis, and intratumor immune infiltrates. Additionally, tumor samples underwent quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry. Spearman correlations (or logistic regression) were performed between CRF/muscle strength and the abovementioned variables. Proteins significantly correlated with CRF or muscle strength were mapped into protein–protein interaction (PPI) networks using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Results: CRF was inversely correlated with clinical severity score (r=–0.657, p=0.020). Of 6,840 identified tumor proteins, 76 correlated significantly with CRF (19 positively, 57 negatively), whereas 194 correlated with muscle strength (97 positively, 97 negatively). Proteins correlated with CRF were primarily involved in metabolic and structural pathways, including angiotensinogen and elastin. In turn, muscle strength-associated proteins were more abundant, and included keratin family proteins (e.g., keratin, type I cytoskeletal 14 and type II cytoskeletal 5), proteins involved in cell adhesion (e.g., desmoglein-1-alpha), and translational regulators (e.g., eukaryotic initiation factor 4A). Network analysis revealed significant enrichment in structural organization and cellular adhesion pathways. Conclusions: Besides the association of CRF with clinical severity of the tumor, distinct novel tumor proteomic signatures associated with CRF and muscle strength were identified, highlighting potential mechanisms linking physical fitness with childhood cancer biology.</p>}},
  author       = {{Santos-Lozano, Alejandro and Plaza-Florido, Abel and Carrera-Bastos, Pedro and Pérez-Prieto, Inmaculada and Hernández-Belmonte, Alejandro and Kamalinejad, Fatemeh and Gálvez, Beatriz G. and López, Juan A. and Lumbreras, Jorge and Rincón-Castanedo, Cecilia and Martín-Ruiz, Asunción and Fleck, Steven J. and López-Soto, Alejandro and Yanguas-Casás, Natalia and Pinós, Tomàs and Lucia, Alejandro and Fiuza-Luces, Carmen}},
  issn         = {{0195-9131}},
  keywords     = {{CANCER; CARDIORESPIRATORY FITNESS; EXERCISE; MUSCLE STRENGTH; ONCOLOGY; TUMOR BIOLOGY; TUMOR IMMUNE INFILTRATES}},
  language     = {{eng}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Medicine and Science in Sports and Exercise}},
  title        = {{Tumor Signatures of Physical Fitness : Insights from a Preclinical Model}},
  url          = {{http://dx.doi.org/10.1249/MSS.0000000000003836}},
  doi          = {{10.1249/MSS.0000000000003836}},
  year         = {{2025}},
}