title: Potential roles of bone morphogenetic protein (BMP)-9 in human liver diseases.
abstract: Bone morphogenetic proteins (BMP-2 to BMP-15) belong to the Transforming Growth Factor (TGF)-β superfamily and, besides their well-documented roles during embryogenesis and bone formation, some of them have recently been described to be involved in the pathogenesis of different organs, including the liver. The role of BMPs in liver damage responses including hepatocellular carcinoma (HCC) development has only begun to be addressed and strong evidence supports the concept of a pro-tumorigenic role of BMP signaling in HCC cells. BMP-9 (also termed Growth and Differentiation Factor (GDF)-2) represents the most recently discovered member of the BMP family. We have previously demonstrated that in HCC patient samples BMP-9 expression was positively associated with the tumor seize ("T stage") and that it enhanced cell migration and induced epithelial to mesenchymal transition (EMT) in HCC cells in vitro. In another study we recently found that BMP-9 promotes growth in HCC cells, but not in non-transformed hepatocytes. Published as well as unpublished results obtained with primary hepatocytes support the concept of a dual function of BMP-9 in the liver: while in primary, non-malignant cells BMP-9 stabilizes the epithelial phenotype and inhibits proliferation, in HCC cells it induces cell growth and the acquisition of a migratory phenotype. In this review article we summarize current knowledge about BMPs in liver diseases, with special focus on the role of BMP-9 in HCC development and progression, that may provide new clues for a better understanding of the contribution of BMP-signaling to chronic liver diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University of Madrid, San Carlos Clinical Hospital Health Research Institute (IdISSC), Madrid 28040, Spain. bm.herrera@farm.ucm.es.
authors.forename: Blanca
authors.initials: B
authors.lastname: Herrera
authors.affiliation: Department of Medicine II, Section Molecular Hepatology-Alcohol Associated Diseases, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany. steven.dooley@medma.uni-heidelberg.de.
authors.forename: Steven
authors.initials: S
authors.lastname: Dooley
authors.affiliation: Department of Medicine II, Section Molecular Hepatology-Alcohol Associated Diseases, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany. katja.breitkopf@medma.uni-heidelberg.de.
authors.forename: Katja
authors.initials: K
authors.lastname: Breitkopf-Heinlein
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D051785:Smad Proteins