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Updated: Jul 9, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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Published on: September 12, 2019

Catecholamines Activate a Tumour Progression Program in Differentiated Tumour Hepatocytes.

Elise Lelou1, Claudine Rauch1, Hélène Dubois-Pot-Schneider2

  • 1INSERM, INRAE, Institut NuMeCan (Nutrition, Metabolisms and Cancer), University of Rennes, Rennes, France.

Liver International : Official Journal of the International Association for the Study of the Liver
|July 8, 2026
PubMed
Summary

Sympathetic nerves and catecholamines promote aggressive hepatocellular carcinoma (HCC) by activating pathways linked to retro-differentiation and epithelial-to-mesenchymal transition in tumor hepatocytes. This highlights potential therapeutic targets for HCC progression.

Keywords:
differentiated HepaRG‐hepatocytesepinephrinehepatocellular carcinomanorepinephrinesympathetic innervationα1A‐ and β2‐adrenoreceptors

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Published on: September 30, 2021

Area of Science:

  • Hepatocellular Carcinoma Research
  • Cancer Biology
  • Neuro-Oncology

Background:

  • The sympathetic nervous system influences cancer progression, including hepatocellular carcinoma (HCC).
  • The precise role of sympathetic innervation and catecholamines in HCC hepatocyte behavior is not well understood.
  • This study investigates the impact of sympathetic fibers and catecholamines on HCC progression.

Purpose of the Study:

  • To investigate the role of sympathetic fibers and catecholamines in HCC progression.
  • To understand how catecholamines affect tumor hepatocyte behavior.
  • To identify potential therapeutic targets by elucidating the sympathetic nervous system-HCC interplay.

Main Methods:

  • Sympathetic nerve distribution was mapped in human HCC samples using multiplex immunofluorescence.
  • Adrenergic receptor (ADR) expression and catecholamine metabolism were assessed in HCC cell lines.
  • The effects of catecholamines on gene/protein expression and metabolic pathways were studied in HepaRG-hepatocytes and primary human hepatocytes (PHH), with clinical relevance evaluated using transcriptomics datasets.

Main Results:

  • Abundant sympathetic fibers were found near the HCC invasion front.
  • Differentiated HepaRG-hepatocytes express α1- and β2-ADR and metabolize catecholamines.
  • Catecholamine exposure induced inflammation, proliferation, extracellular matrix remodeling, and primed epithelial-to-mesenchymal transition in hepatocytes, mirroring aggressive HCC subclasses.

Conclusions:

  • Catecholamines induce an aggressive phenotype in tumor hepatocytes at the invasive front, suggesting a role in HCC progression.
  • The interaction between the sympathetic nervous system and HCC presents potential therapeutic avenues.
  • Targeting this neuro-humoral axis may offer novel strategies for managing aggressive HCC.