title: Chronic liver inflammation and hepatocellular carcinogenesis are independent of S100A9.
abstract: 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 S100a9 were crossed with the Mdr2(-/-) model, a prototype of inflammation-induced HCC formation. S100a9(-/-) Mdr2(-/-) (dKO) mice displayed no significant differences in tumor incidence or multiplicity compared to Mdr2(-/-) animals. Chronic liver inflammation, fibrosis and oval cell activation were not affected upon S100a9 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.
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.forename: Lars
authors.initials: L
authors.lastname: Wiechert
authors.forename: Ana
authors.initials: A
authors.lastname: Stojanovic
authors.forename: Thomas
authors.initials: T
authors.lastname: Longerich
authors.forename: Silke
authors.initials: S
authors.lastname: Marhenke
authors.forename: Nancy
authors.initials: N
authors.lastname: Hogg
authors.forename: Arndt
authors.initials: A
authors.lastname: Vogel
authors.forename: Adelheid
authors.initials: A
authors.lastname: Cerwenka
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Jochen
authors.initials: J
authors.lastname: Hess
authors.forename: Peter
authors.initials: P
authors.lastname: Angel
mesh_terms: D000818:Animals; D040502:Calgranulin B / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D055786:Gene Knockout Techniques; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D040502:Calgranulin B; D039841:Leukocyte L1 Antigen Complex; C576329:S100A9 protein, mouse
keywords: damage-associated molecular pattern molecules; hepatocellular carcinoma; liver fibrosis; oval cell