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| Status |
Public on May 12, 2014 |
| Title |
Induction of hepatocellular carcinoma through activation of stromal cells in Pdgf-c transgenic mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Liver cirrhosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet the mechanisms by which cirrhosis predisposes patients to tumorigenesis are not well understood. Transgenic mice expressing platelet-derived growth factor C (Pdgf-c) under the control of the albumin promoter provide a unique animal model that mimics the step-wise disease progression in humans from fibrosis to HCC. The livers of Pdgf-c Tg mice show evidence of liver injury, including inflammation, proliferation, fibrosis and steatosis, and as the mice age, angiogenesis and dysplasia. Eighty-five percent of these mice develop HCC spontaneously, and have reduced survival that is related to their liver pathology. Through measurement of protein, RNA, and histological markers, we provide evidence to support the hypothesis that changes in liver stromal cells play an essential role in tumorigenesis in this model. A paracrine signaling model is proposed where ectopic expression of Pdgf-c in hepatocytes results in activation of hepatic stellate cells, which subsequently activates endothelial and Kupffer cells. Activation of these non-parenchymal cells promotes the release of hepatocyte growth factors that, together with changes in extracellular matrix, lead to the formation of HCC. Pdgf-c Tg mice provide a useful pre-clinical model in which to test novel drugs for chronic liver disease and HCC that focus on blocking the processes that alter the liver's fibrotic microenvironment.
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| Overall design |
Two strains of mice, C57BL/6 and C57/BL6 Pdgf-c transgenic, were analyzed to see if liver stromal cells play an essential role in tumorigenesis.
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| Contributor(s) |
Wright JH, Johnson MM, Yeh MM, Bauer RL, Hudkins KL, Gilbertson DG, Bammler TK, Beyer RP, Fausto N, Campbell JS |
| Citation(s) |
23929039, 26632601 |
| Submission date |
May 23, 2012 |
| Last update date |
Mar 04, 2019 |
| Contact name |
James William MacDonald |
| E-mail(s) |
jmacdon@uw.edu
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| Organization name |
University of Washington
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| Department |
Environmental and Occupational Health Sciences
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| Street address |
4225 Roosevelt Way NE
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98105-6099 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA167517 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE38199_RAW.tar |
63.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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