UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Cytosolic and nuclear caspase-8 have opposite impact on survival after liver resection for hepatocellular carcinoma

Koschny, R; Brost, S; Hinz, U; Sykora, J; Batke, EM; Singer, S; Breuhahn, K; ... Ganten, TM; + view all (2013) Cytosolic and nuclear caspase-8 have opposite impact on survival after liver resection for hepatocellular carcinoma. BMC Cancer , 13 , Article 532. 10.1186/1471-2407-13-532. Green open access

[thumbnail of 1471-2407-13-532.pdf]
Preview
PDF
1471-2407-13-532.pdf

Download (2MB)
[thumbnail of ePUB version] Other (ePUB version)
1471-2407-13-532.epub

Download (316kB)

Abstract

Background An imbalance between proliferation and apoptosis is one of the main features of carcinogenesis. TRAIL (TNF-related apoptosis-inducing ligand) induces apoptosis upon binding to the TRAIL death receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2, whereas binding to TRAIL-R3 and TRAIL-R4 might promote cell survival and proliferation. The anti-tumor activity of TRAIL-R1 and TRAIL-R2 agonists is currently investigated in clinical trials. To gain further insight into the regulation of apoptosis in hepatocellular carcinoma (HCC), we investigated the TRAIL pathway and the regulators of apoptosis caspase-8, Bcl-xL and Mcl-1 in patients with HCC regarding patient survival. Methods We analyzed 157 hepatocellular carcinoma patients who underwent partial liver resection or orthotopic liver transplantation and healthy control liver tissue using immunohistochemistry on tissue microarrays for the expression of TRAIL-R1 to TRAIL-R4, caspase-8, Bcl-xL and Mcl-1. Immunohistochemical data were evaluated for potential associations with clinico-pathological parameters and survival. Results Whereas TRAIL-R1 was downregulated in HCC in comparison to normal liver tissue, TRAIL-R2 and –R4 were upregulated in HCC, especially in G2 and G3 tumors. TRAIL-R1 downregulation and upregulation of TRAIL-R2 and TRAIL-R4 correlated with tumor dedifferentiation (G2/G3). TRAIL-R3, Bcl-xL and Mcl-1 showed no differential expression in tumor tissue compared to normal tissue. The expression levels of TRAIL receptors did not correlate with patient survival after partial hepatectomy. Interestingly, in tumor tissue, but not in normal hepatocytes, caspase-8 showed a strong nuclear staining. Low cytosolic and high nuclear staining intensity of caspase-8 significantly correlated with impaired survival after partial hepatectomy, which, for cytosolic caspase-8, was independent from tumor grade. Conclusions Assessment of TRAIL-receptor expression patterns may have therapeutic implications for the use of TRAIL receptor agonists in HCC therapy. Tumor-specific nuclear localisation of caspase-8 in HCC suggests an apoptosis-independent function of caspase-8 and correlates with patient survival.

Type: Article
Title: Cytosolic and nuclear caspase-8 have opposite impact on survival after liver resection for hepatocellular carcinoma
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1471-2407-13-532
Publisher version: http://dx.doi.org/10.1186/1471-2407-13-532
Language: English
Additional information: © 2013 Koschny et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: HCC, Apoptosis, TRAIL receptors, Nuclear caspase-8
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1426308
Downloads since deposit
155Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item