title: A pro-tumorigenic function of S100A8/A9 in carcinogen-induced hepatocellular carcinoma.
abstract: Human hepatocellular carcinoma (HCC) is a heterogeneous disease, driven by different risk factors and presenting diverse clinicopathological features and outcomes. Epidemiological and experimental data indicate that the damage-associated molecular pattern molecules S100A8 and S100A9, forming a heterodimer called calprotectin, might be critically involved in HCC development. However, deletion of S100a9 in an inflammation- and cirrhosis-driven mouse model did not show any impairment in liver tumorigenesis, most likely due to functional compensation by other inflammatory cytokines. Here, we investigated the effect of calprotectin ablation in mice treated with diethylnitrosamine, a carcinogen-driven HCC model mimicking cancer development caused by acute liver damage in the absence of prominent chronic inflammation and tissue damage. We found that tumor cell proliferation was diminished in the absence of S100A8/A9, leading to significant reduction of tumor size. Our results demonstrate that calprotectin is required for the progression of non-inflammation driven liver tumor and might represent a therapeutic target for the treatment of HCC formed in non-cirrhotic liver.
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Aurora
authors.initials: A
authors.lastname: De Ponti
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Wiechert
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Schneller
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Pusterla
authors.affiliation: Institute of Pathology University Hospital RWTH Aachen, Germany; Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Longerich
authors.affiliation: Leukocyte Adhesion Laboratory, London Research Institute Cancer Research UK, London, UK.
authors.forename: Nancy
authors.initials: N
authors.lastname: Hogg
authors.affiliation: Department of Hepatology, Medical School Hannover, Hannover, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Vogel
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: Research Group Molecular Mechanisms of Head and Neck Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Otolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Hess
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: p.angel@dkfz-heidelberg.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Angel
mesh_terms: D000818:Animals; D040501:Calgranulin A / Q000235:genetics*; D040502:Calgranulin B / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B
keywords: Damage-associated molecular pattern molecule; Diethylnitrosamine; Hepatocellular carcinoma; S100A8; S100A9