Int. J. Mol. Sci. 2014, 15(4), 5199-5220; doi:10.3390/ijms15045199
Review

Potential Roles of Bone Morphogenetic Protein (BMP)-9 in Human Liver Diseases

1email, 2email and 2,* email
Received: 5 February 2014; in revised form: 7 March 2014 / Accepted: 17 March 2014 / Published: 25 March 2014
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 Published as well as unpublished results obtained with primary hepatocytes support the concept of a dual function of BMP-9 in the liver: while in primary, non-malignant cells BMP-9 stabilizes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.
Keywords: BMP-9; Hepatocellular carcinoma; signaling; physiology; liver; hepatocytes; hepatic stellate cells; angiogenesis; therapy
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MDPI and ACS Style

Herrera, B.; Dooley, S.; Breitkopf-Heinlein, K. Potential Roles of Bone Morphogenetic Protein (BMP)-9 in Human Liver Diseases. Int. J. Mol. Sci. 2014, 15, 5199-5220.

AMA Style

Herrera B, Dooley S, Breitkopf-Heinlein K. Potential Roles of Bone Morphogenetic Protein (BMP)-9 in Human Liver Diseases. International Journal of Molecular Sciences. 2014; 15(4):5199-5220.

Chicago/Turabian Style

Herrera, Blanca; Dooley, Steven; Breitkopf-Heinlein, Katja. 2014. "Potential Roles of Bone Morphogenetic Protein (BMP)-9 in Human Liver Diseases." Int. J. Mol. Sci. 15, no. 4: 5199-5220.

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