Establishment and Phenotypic Validation of an Immunocompetent Mouse Model of Neuroblastoma-Associated Cachexia

DOI: https://doi.org/10.62517/jmhs.202605317

Author(s)

Yuchen Ke1, Keyi Liu1, Jiayu Wang1, Xiaoran Li2, Yibakezi Abula1, Wanqi Li1, Lei Zhang1, Yan Zhang1, Biqin Dong2, Ling Tao1,*

Affiliation(s)

1Department of Nutrition and Food Hygiene, School of Public Health, Institution of Nutrition, Fudan University, Shanghai, China 2Yiwu Research Institute, Fudan University, Shanghai, China *Corresponding Author

Abstract

Neuroblastoma (NB) represents the most prevalent extracranial solid malignancy in children. High-risk NB patients frequently develop cancer cachexia, a life-threatening metabolic disorder characterized by skeletal muscle wasting and fat loss. However, NB-associated cachexia remains understudied. This study established a preclinical model of NB-induced cachexia. Immunocompetent male A/J Gpt mice were subcutaneously inoculated with 1×10⁶ murine Neuro-2a cells to establish the NB cachexia model. Longitudinal phenotypic characterization included serial monitoring of body weight, food and water consumption, and grip strength. Histopathological analysis was performed to confirm tissue atrophy. Circulating pro-inflammatory cytokines (IL‑1β, IL‑6, TNF‑α), and tissue gene transcript levels (Fbxo32, Trim63, Myh4, Pnpla2, Lipe and Plin1) were quantified to characterise the molecular alterations underlying tumor-induced cachexia. The model reproduced core clinical features of cancer cachexia. Tumor-bearing mice entered cachexia progression on Day 12 post-inoculation, exhibiting progressive body weight loss, reduced food intake, impaired motor function, significant bilateral skeletal muscle atrophy, and extensive depletion of white and brown adipose tissues. Histopathological analysis confirmed a reduction in myofiber cross-sectional area and marked adipocyte shrinkage. Elevated circulating pro-inflammatory cytokines and coordinated transcriptional dysregulation of muscle atrophy and adipose lipolysis programmes suggest skeletal muscle and adipose tissue lost We have established and validated a preclinical model of NB-induced cachexia that recapitulates key clinical phenotypes. This model provides a platform for investigating disease mechanisms, identifying diagnostic biomarkers, and developing targeted therapies.

Keywords

Neuroblastoma; Cancer Cachexia; Adipose Tissue Loss; Skeletal Muscle Atrophy; Pediatric Oncology

References

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