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| Status |
Public on Nov 21, 2011 |
| Title |
Comparison of two hepatocellular cancer cell lines with distinct properties regarding epithelial-mesenchymal transition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The epithelial to mesenchymal transition (EMT) of malignant hepatocytes is a crucial event in hepatocellular carcinoma (HCC) progression and recurrence. We aimed to establish a human model of EMT to examine drug efficacy and specificity in HCC progression. Human HCC cell populations were characterized by immunofluorescence analysis, migration and invasion assays, array comparative genomic hybridization, whole-genome expression profiling and promoter methylation. Therapeutic agents clinically used against HCC were examined for efficacy by determination of IC50 values. Liver cancer cell lines showed either an epithelial or mesenchymal phenotype of which latter showed strong migratory and invasive abilities in vitro. The common cellular origin of both cell types indicated that mesenchymal HCC cells have been derived from epithelial hepatocytes through EMT in the HCC patient. Drug exposure of mesenchymal HCC cells showed higher resistance to the targeted therapeutic agents sorafenib and erlotinib as compared to epithelial HCC cells, which were slightly more resistant to cytostatic drugs. Most remarkably, combined treatment with doxorubicin and sorafenib caused increased susceptibility of both HCC cell types resulting in enhanced drug efficacy. Taken together, this novel model of human HCC allows to monitor the differential effect of liver cancer progression on drug efficacy in pre-clinical studies.
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| Overall design |
hepatocellular carcinoma cell lines HCC-1.2 and HCC-1.1 cells, referred to as 3p and 3sp cells, respectively, were isolated from one HCC patient as described ( Sagmeister S, Eisenbauer M, Pirker C, et al. New cellular tools reveal complex epithelial-mesenchymal interactions in hepatocarcinogenesis. Br J Cancer 2008;99(1):151-9.). 3p cells of passages 10 to 12 and 3sp cells of passages 7 to 13 are termed 3p early and 3sp early, respectively. 3p cells between passage 71 and 76 and 3sp from passage 72 to 87 were termed 3p late and 3sp late, respectively
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| Contributor(s) |
van Zijl F, Bilban M, Mikulits W |
| Citation(s) |
21364009 |
| |
| Submission date |
Jan 03, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Martin Bilban |
| E-mail(s) |
[email protected]
|
| Phone |
++43 (0)1 40400 6441
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| Organization name |
Medical University of Vienna
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| Department |
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| Street address |
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| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA136839 |
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