Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Sagmeister, S; Eisenbauer, M; Pirker, C; Mohr, T; Holzmann, K; Zwickl, H; Bichler, C; Kandioler, D; Wrba, F; Mikulits, W; Gerner, C; Shehata, M; Majdic, O; Streubel, B; Berger, W; Micksche, M; Zatloukal, K; Schulte-Hermann, R; Grasl-Kraupp, B.
New cellular tools reveal complex epithelial-mesenchymal interactions in hepatocarcinogenesis.
Br J Cancer. 2008; 99(1):151-159
Doi: 10.1038/sj.bjc.6604440
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- Co-Autor*innen der Med Uni Graz
- Zatloukal Kurt
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- Abstract:
- To enable detailed analyses of cell interactions in tumour development, new epithelial and mesenchymal cell lines were established from human hepatocellular carcinoma by spontaneous outgrowth in culture. We obtained several hepatocarcinoma (HCC)-, B-lymphoblastoid (BLC)-, and myofibroblastoid (MF)-lines from seven cases. In-depth characterisation included cell kinetics, genotype, tumourigenicity, expression of cell-type specific markers, and proteome patterns. Many functions of the cells of origin were found to be preserved. We studied the impact of the mesenchymal lines on hepatocarcinogenesis by in vitro assays. BLC- and MF-supernatants strongly increased the DNA replication of premalignant hepatocytes. The stimulation by MF-lines was mainly attributed to HGF secretion. In HCC-cells, MF-supernatant had only minor effects on cell growth but enhanced migration. MF-lines also stimulated neoangiogenesis through vEGF release. BLC-supernatant dramatically induced death of HCC-cells, which could be largely abrogated by preincubating the supernatant with TNFbeta-antiserum. Thus, the new cell lines reveal stage-specific stimulatory and inhibitory interactions between mesenchymal and epithelial tumour cells. In conclusion, the new cell lines provide unique tools to analyse essential components of the complex interplay between the microenvironment and the developing liver cancer, and to identify factors affecting proliferation, migration and death of tumour cells, neoangiogenesis, and outgrowth of additional malignancy.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Carcinoma, Hepatocellular - physiopathology
- Cell Communication -
- Cell Line, Tumor -
- Epithelial Cells -
- Humans -
- Liver Neoplasms - physiopathology
- Mice -
- Rats -
- Find related publications in this database (Keywords)
- hepatocarcinogenesis
- tumour stroma
- epithelial-mesenchymal interactions