Expression of TLR-2 in hepatocellular carcinoma is associated with tumour proliferation,angiogenesis and Caspase-3 expression |
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| Institution: | 1. Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden;2. Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy;3. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA;4. Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany;5. Department of General Surgery and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel, Germany;6. Medical Department I, University Hospital Dresden, Dresden, Germany;7. Department of Medicine, Duke University Medical Center, Durham, NC, USA;8. Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA |
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| Abstract: | AimsUnlike other Toll-like receptors (TLRs), the role of toll like receptor 2 (TLR-2) in the pathogenesis of chronic liver disease and hepatocellular carcinoma (HCC) is not well studied. We, therefore, set out to investigate the expression of TLR-2 in different chronic liver disease states along with other markers of cell death, cellular proliferation and tissue vascularisationMethods and resultsImmunohistochemistry was performed on liver tissue microarrays comprising hepatitis, cirrhosis and HCC patient samples using antibodies against TLR-2, Ki-67, Caspase-3 and VEGF. This was done in order to characterise receptor expression and translocation, apoptosis, cell proliferation and vascularisation. Cytoplasmic TLR-2 expression was found to be weak in 5/8 normal liver cases, 10/19 hepatitis cases and 8/21 cirrhosis patients. Moderate to strong TLR-2 expression was observed in some cases of hepatitis and cirrhosis. Both, nuclear and cytoplasmic TLR-2 expression was present in HCC with weak intensity in 11/41 cases, and moderate to strong staining in 19/41 cases. Eleven HCC cases were TLR-2 negative. Surprisingly, both cytoplasmic and nuclear TLR-2 expression in HCC were found to significantly correlate with proliferative index (r = 0.24 and 0.37), Caspase-3 expression (r = 0.27 and 0.38) and vascularisation (r = 0.56 and 0.23). Further, nuclear TLR-2 localisation was predominant in HCC, whereas cytoplasmic expression was more prevalent in hepatitis and cirrhosis. Functionally, treatment of HUH7 HCC cells with a TLR-2 agonist induced the expression of cellular proliferation and vascularisation markers CD34 and VEGF.ConclusionsOur results demonstrate a positive correlation between the expression of TLR-2 and other markers of proliferation and vascularisation in HCC which suggests a possible role for TLR-2 in HCC pathogenesis |
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| Keywords: | TLR2 HCC proliferation vascularisation |
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