{"doi":"10.1002/ijc.29282","title":"Chronic liver inflammation and hepatocellular carcinogenesis are independent of <scp>S</scp>100<scp>A</scp>9","abstract":"<jats:p>The S100A8/A9 heterodimer (calprotectin) acts as a danger signal when secreted into the extracellular space during inflammation and tissue damage. It promotes proinflammatory responses and drives tumor development in different models of inflammation‐driven carcinogenesis. S100A8/A9 is strongly expressed in several human tumors, including hepatocellular carcinoma (HCC). Apart from this evidence, the role of calprotectin in hepatocyte transformation and tumor microenvironment is still unknown. The aim of this study was to define the function of S100A8/A9 in inflammation‐driven HCC. Mice lacking <jats:italic>S100a9</jats:italic> were crossed with the <jats:italic>Mdr2<jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup></jats:italic> model, a prototype of inflammation‐induced HCC formation. <jats:italic>S100a9<jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup> Mdr2<jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup></jats:italic> (<jats:italic>dKO</jats:italic>) mice displayed no significant differences in tumor incidence or multiplicity compared to <jats:italic>Mdr2<jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup></jats:italic> animals. Chronic liver inflammation, fibrosis and oval cell activation were not affected upon <jats:italic>S100a9</jats:italic> deletion. Our data demonstrate that, although highly upregulated, calprotectin is dispensable in the onset and development of HCC, and in the maintenance of liver inflammation.</jats:p>","journal":"International Journal of Cancer","year":2015,"id":687343,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1795654,"name":"Lars Wiechert","orcid":null,"position":1,"is_corresponding":false},{"id":75420,"name":"Ana Stojanovic","orcid":"0000-0001-9503-2256","position":2,"is_corresponding":false},{"id":84696,"name":"Thomas Longerich","orcid":"0000-0001-8888-1030","position":3,"is_corresponding":false},{"id":1795655,"name":"Silke Marhenke","orcid":null,"position":4,"is_corresponding":false},{"id":1795656,"name":"Nancy Hogg","orcid":null,"position":5,"is_corresponding":false},{"id":616403,"name":"Arndt Vogel","orcid":null,"position":6,"is_corresponding":false},{"id":75421,"name":"Adelheid Cerwenka","orcid":"0000-0001-6977-3536","position":7,"is_corresponding":false},{"id":41024,"name":"Peter Schirmacher","orcid":"0000-0002-0950-3339","position":8,"is_corresponding":false},{"id":1736262,"name":"Jochen Hess","orcid":null,"position":9,"is_corresponding":false},{"id":1570254,"name":"Peter Angel","orcid":null,"position":10,"is_corresponding":false},{"id":1795653,"name":"Aurora De Ponti","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Chronic liver inflammation and hepatocellular carcinogenesis are independent of <scp>S</scp>100<scp>A</scp>9","abstract":"<jats:p>The S100A8/A9 heterodimer (calprotectin) acts as a danger signal when secreted into the extracellular space during inflammation and tissue damage. It promotes proinflammatory responses and drives tumor development in different models of inflammation‐driven carcinogenesis. S100A8/A9 is strongly expressed in several human tumors, including hepatocellular carcinoma (HCC). Apart from this evidence, the role of calprotectin in hepatocyte transformation and tumor microenvironment is still unknown. The aim of this study was to define the function of S100A8/A9 in inflammation‐driven HCC. Mice lacking <jats:italic>S100a9</jats:italic> were crossed with the <jats:italic>Mdr2<jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup></jats:italic> model, a prototype of inflammation‐induced HCC formation. <jats:italic>S100a9<jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup> Mdr2<jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup></jats:italic> (<jats:italic>dKO</jats:italic>) mice displayed no significant differences in tumor incidence or multiplicity compared to <jats:italic>Mdr2<jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup></jats:italic> animals. Chronic liver inflammation, fibrosis and oval cell activation were not affected upon <jats:italic>S100a9</jats:italic> deletion. Our data demonstrate that, although highly upregulated, calprotectin is dispensable in the onset and development of HCC, and in the maintenance of liver inflammation.</jats:p>","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25331529","pmcid":null,"openalex_id":"https://openalex.org/W2112680379","authors":[],"funders":[{"funder_name":"Helmholtz Alliance Preclinical Comprehensive Cancer Center","grant_id":"HA-305","title":null},{"funder_name":"the Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) and Israel's Ministry of Science","grant_id":"Ca-130; Ca-147","title":null},{"funder_name":"German Research Foundation (SFB Transregio 77)","grant_id":"","title":null}],"total_grants":3,"fwci":0.13,"citation_percentile":0.51737364,"influential_citations":0,"citation_trend":[{"year":2015,"count":1},{"year":2018,"count":3},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fijc.29282","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.29282","host_type":"publisher"},{"url":"https://doi.org/10.1002/ijc.29282","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25331529","host_type":"repository"}],"fields_of_study":["S100 Proteins and Annexins","Immune Response and Inflammation","Protease and Inhibitor Mechanisms","Animals","Calgranulin B","Cell Transformation, Neoplastic","Gene Knockout Techniques","Humans","Inflammation","Leukocyte L1 Antigen Complex","Liver","Liver Neoplasms, Experimental","Mice","Mice, Knockout"],"mesh_terms":["Animals","Cell Transformation, Neoplastic","Humans","Inflammation","Liver","Liver Neoplasms, Experimental","Mice, Knockout","Leukocyte L1 Antigen Complex","Calgranulin B","Mice","Gene Knockout Techniques"],"keywords":["Inflammation","S100A9","Hepatocellular carcinoma","Carcinogenesis","Calprotectin","Fibrosis","S100A8","Proinflammatory cytokine","Cancer research","Hepatocyte","Biology","Tumor microenvironment","Medicine","Immunology","Pathology","Cancer","Internal medicine","Liver fibrosis","Oval cell","Damage-associated Molecular Pattern Molecules"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T21:49:06.078602Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}