[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-353251-105":59,"doc-detail-353251-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","catecholamines-activate-a-tumour-progression-program-in-differentiated-tumour-hepatocytes","Catecholamines Activate a Tumour Progression Program in Differentiated Tumour Hepatocytes","","Sympathetic innervation and catecholamines influence the progression and aggressiveness of several cancers, yet their direct effects on tumour hepatocyte behaviour in hepatocellular carcinoma (HCC) remain unclear. This study mapped sympathetic fibres in human HCC tissues, assessed adrenergic receptors and catecholamine-degrading enzymes in multiple HCC and hepatoblastoma cell lines, and tested catecholamine-driven gene, protein, and metabolic changes in differentiated HepaRG-hepatocytes.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/catecholamines-activate-a-tumour-progression-program-in-differentiated-tumour-hepatocytes/353251/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/catecholamines-activate-a-tumour-progression-program-in-differentiated-tumour-hepatocytes/353251.png","ImageObject",300,407,{"name":92,"@type":93},"Anna Hans","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What was the study’s main goal regarding catecholamines and HCC?","Question",{"text":113,"@type":114},"To determine how sympathetic fibres and catecholamines affect the progression behaviour of tumour hepatocytes in hepatocellular carcinoma.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were sympathetic nerves and adrenergic targets assessed in the study?",{"text":118,"@type":114},"Sympathetic nerve distribution was mapped in human HCC samples using multiplex immunofluorescence, and adrenergic receptors plus catecholamine degradation enzymes were evaluated in HCC and hepatoblastoma cell lines.",{"name":120,"@type":111,"acceptedAnswer":121},"What effects did catecholamines have on differentiated tumour hepatocytes?",{"text":122,"@type":114},"Catecholamine exposure activated inflammation, cell proliferation, and extracellular matrix remodelling pathways linked to retro-differentiation and primed epithelial-to-mesenchymal transition, producing an aggressive phenotype.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},353251,1790181571,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},5909892332657,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Liver International  \nORIGINAL ARTICLE  OPEN ACCESS   \nCatecholamines Activate a Tumour Progression Program in Differentiated Tumour Hepatocytes  \nElise Lelou1 | Claudine Rauch1 | Hélène Dubois-Pot-Schneider2 | Marjorie Dufresne1 | Abolfazl Zekri Yazdi1 | Maelle Guillout3  | Luis Cano1 | Lise Desquilles1 | Nicolas Nesseler1,4 | Marc Bourgeois5 | Claude Bendavid1,5 | Julie Massart1 | Orlando Musso1 | Anne Corlu1 | Caroline Aninat1   \n1INSERM, INRAE, Institut NuMeCan (Nutrition, Metabolisms and Cancer), University of Rennes, Rennes, France | 2Université de Lorraine, CNRS, CRAN, Nancy, France | 3Core Facility H2P2, CNRS, INSERM, UMS Biosit, University of Rennes, Rennes, France | 4Department of Anesthesia and Critical Care, Pontchaillou, CHU Rennes, University Hospital of Rennes, Rennes, France | 5Department of Biochemistry, CHU Rennes, Pontchaillou University Hospital, Rennes, France  \nCorrespondence: Caroline Aninat ([caroline.aninat@univ-rennes.fr](caroline.aninat@univ-rennes.fr))  \nReceived: 18 July 2025 | Revised: 11 April 2026 | Accepted: 16 June 2026  \nHandling Editor: Dr. Alejandro Forner  \nKeywords: α1A-and β2-adrenoreceptors | differentiated HepaRG-hepatocytes | epinephrine | hepatocellular carcinoma | norepinephrine | sympathetic  \ninnervation  \nABSTRACT  \nBackground and Aims: The sympathetic nervous system is involved in the progression and aggressiveness of several cancers, including hepatocellular carcinoma (HCC) . However, the specific effects of sympathetic innervation and catecholamines on tumour hepatocyte behaviour remain poorly understood. In this study, we aimed to investigate the role of sympathetic fibres and catecholamines in the progression of HCC.  \nMethods: The distribution of sympathetic nerves was mapped in 10 human HCC samples using multiplex immunofluorescence labeling. Adrenergic receptors (ADR) and enzymes involved in catecholamine degradation were assessed in three HCC (HepaRG, BC2, Huh-7) and one hepatoblastoma (HepG2) cell lines. The impact of catecholamines on gene and protein expression and metabolic pathways was assessed in differentiated HepaRG-hepatocytes, and the results were verified in primary human hepatocyte (PHH) cultures. The clinical relevance of the findings was evaluated in two transcriptomics datasets.  \nResults: Abundant and tortuous sympathetic fibres were detected in non-tumour liver tissues adjacent to the HCC invasion front. Differentiated HepaRG-hepatocytes expressed both α1-and β2-ADR and metabolized catecholamines to normetanephrine, metanephrine, and vanillylmandelic acid. In these cells, catecholamine exposure activated inflammation, cell proliferation, and extracellular matrix remodelling pathways associated with retro-differentiation and primed epithelial-to-mesenchymal transition. The catecholamine-induced program was detected in aggressive, ECM/STEM HCC subclasses with poor patient prognosis. Conclusions: Catecholamines induce an aggressive phenotype in differentiated tumour hepatocytes localized at the invasive front, suggesting their involvement in cancer progression. Understanding the interplay between the sympathetic nervous system and HCC may offer novel therapeutic opportunities.  \n\n| Abbreviations: ADR, adrenergic receptor or adrenoceptors; BrdU, bromodeoxyuridine; COMT, catecholamine-O-methyltransferase; DEGs, differentially expressed genes; DMSO, dimethylsulfoxide; ECM, extracellular matrix organization; EMT, epithelial-to-mesenchymal transition; FBS, fetal bovine serum; HCC, hepatocellular carcinoma; IL-6, interleukine-6; JAK, Janus kinase; KEGG, Kyoto Encyclopedia of Genes and Genomes; MAO, monoamine oxidase; NF-κB, nuclear factor-kappa B; PBS, phosphate buffer saline; PGP9.5, protein gene product 9.5; PHH, primary human hepatocytes; PI3K, phosphoinositide-3 kinase; STAT3, signal transducer and activator of transcription 3; TH, tyrosine hydroxylase.\u003Cbr>Marjorie Dufresne and Abolfazl Zekri Yazdi contributed equally to this study. |\n| --- |\n| This is an ope","cbCaijqu7XIBIG1B","https://ap.wps.com/l/cbCaijqu7XIBIG1B","pdf",7809771,14,"English","# Key points\n# Introduction","[{\"question\":\"What was the study’s main goal regarding catecholamines and HCC?\",\"answer\":\"To determine how sympathetic fibres and catecholamines affect the progression behaviour of tumour hepatocytes in hepatocellular carcinoma.\"},{\"question\":\"How were sympathetic nerves and adrenergic targets assessed in the study?\",\"answer\":\"Sympathetic nerve distribution was mapped in human HCC samples using multiplex immunofluorescence, and adrenergic receptors plus catecholamine degradation enzymes were evaluated in HCC and hepatoblastoma cell lines.\"},{\"question\":\"What effects did catecholamines have on differentiated tumour hepatocytes?\",\"answer\":\"Catecholamine exposure activated inflammation, cell proliferation, and extracellular matrix remodelling pathways linked to retro-differentiation and primed epithelial-to-mesenchymal transition, producing an aggressive phenotype.\"}]","Catecholamines Activate a Tumour Progression Program in Differentiated Tumour Hepatocytes | PDF",1790103867,35]