Amann, Thomas and Bataille, Frauke and Spruss, Thilo and Muehlbauer, Marcus and Gaebele, Erwin and Schoelmerich, Juergen and Kiefer, Paul and Bosserhoff, Anja-Katrin and Hellerbrand, Claus (2009) Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma. CANCER SCIENCE, 100 (4). pp. 646-653. ISSN 1349-7006,
Full text not available from this repository. (Request a copy)Abstract
Liver cirrhosis is the main risk factor for the development of hepatocellular carcinoma (HCC). Activated hepatic stellate cells (HSC) are the effector cells of hepatic fibrosis and also infiltrate the HCC stroma where they might play a critical role in HCC progression. Here we aimed to analyze the effects of activated HSC on the proliferation and growth of HCC cell lines in vitro and in vivo. Conditioned media (CM) collected from HSC significantly induced proliferation and migration of HCC cells cultured in monolayers. In a 3-dimensional spheroid coculture system, HSC promoted HCC growth and diminished the extent of central necrosis. In accordance, in vivo simultaneous implantation of HSC and HCC cells into nude mice promoted tumor growth and invasiveness, and inhibited necrosis formation. As potential mechanism of the tumorigenic effects of HSC we identified activation of NFkappaB and extracellular-regulated kinase (ERK) in HCC cells, two signaling cascades that play a crucial role in HCC progression. In summary, our data indicate that stromal HSC promotes HCC progression and suggest the HSC-HCC interaction as an interesting tumor differentiation-independent target for therapy of this highly aggressive cancer. (Cancer Sci 2009; 100: 646-653)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATOCYTE GROWTH-FACTOR; NF-KAPPA-B; TUMOR PROGRESSION; LIVER-CANCER; EXPRESSION; INTERLEUKIN-8; DISEASE; MYOFIBROBLASTS; APOPTOSIS; PATHWAYS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Lehrstuhl für Pathologie Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Sep 2020 08:54 |
| Last Modified: | 18 Sep 2020 08:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29150 |
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