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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 Published as well as unpublished results obtained with primary hepatocytes support the concept of a dual function of BMP-9 in the liver: while in primary, non-malignant cells BMP-9 stabilizes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.

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Projects: A2.2: Regulation of pro-apoptotic and anti-apoptotic responses in hepato..., A2.3: Cross-talk and distinct properties of growth factor signalling reg..., A3.3: Hepatocyte polarity, B2.1: Hepatic stellate cells as source and target for hepatocellular gro..., B2.3: Effect of hepatic stellate cells on hepatocyte polarity and transd..., Showcase HGF and Regeneration, Showcase LPS and Inflammation

Int J Mol Sci
Int J Mol Sci 15(4): 5199-220
29th Mar 2014

Blanca Herrera, Steven Dooley, Katja Breitkopf-Heinlein

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[Steven Dooley] [Katja Breitkopf-Heinlein]

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Views: 1342
  • Created: 31st Mar 2014 at 11:18

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