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| Status |
Public on May 12, 2010 |
| Title |
Epithelial-to-Mesenchymal Transition of Murine PTEN-/- Liver Tumor Cells Promotes Tumor Growth and Invasion |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Background: Epithelial-to-Mesenchymal Transition (EMT) is predicted to play a critical role in tumor progression and metastasis in Hepatocellular Carcinoma. Our goal was to elucidate a mechanism of tumor proliferation and metastasis using a novel murine model of EMT.
Methods: 2×106 liver cells isolated from Ptenloxp/loxp;Alb-Cre+ mice, expanded from a single CD133+CD45- cell clone, Passage 0 (P0), were sequentially transplanted to obtain two passages of tumor cells, Passage 1 and 2 (P1 & P2) . Cells were analyzed for gene expression using microarray and real-time PCR. Functional analysis included cell proliferation, migration, and invasion in-vitro and orthotopic tumor growth and metastasis assays in-vivo.
Results: Although P0, P1, and P2 each formed tumors consistent with mixed liver epithelium, within the P2 cells, two distinct cell types were clearly visible: cells with epithelial morphology similar to the P0 cells, and cells with fibroblastoid morphology. The P2 mesenchymal cells demonstrated increased locomotion on wound healing, increased cell invasion on Matrigel basement membrane, increased EMT associated gene Snail1, Zeb1, and Zeb2 expression, and down-regulated E-cadherin. P2 mesenchymal cells demonstrated significantly faster tumor growth compared to P2 Epithelial counterparts, with peritoneal seeding and invasion of intestine, pancreas, spleen, and lymph nodes. Furthermore, P2 mesenchymal cells secreted high levels of Hepatocyte Growth Factor (HGF), which acted in paracrine fashion to drive epithelial cells to undergo EMT.
Conclusion: EMT is associated with a high rate of liver tumor proliferation, invasion, and metastasis in-vivo, which is driven by HGF in a feed-forward mechanism.
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| Overall design |
Total RNA isolated from subcutaneously transplanted tumors with PTENloxp/loxp;Alb-Cre+ genetic background
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| Contributor(s) |
Ding W, You H, LeBlanc F, Dang H, Rountree CB |
| Citation(s) |
20564331 |
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| Submission date |
Sep 24, 2009 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Wei Ding |
| Organization name |
Pennsylvania State University College of Medicine
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| Department |
Pediatrics
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| Lab |
Rountree Lab
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| Street address |
500 University Drive
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| City |
Hershey |
| State/province |
PA |
| ZIP/Postal code |
17033 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA119597 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE18255_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE18255_RAW.txt.gz |
3.3 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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