Expression of TLR-2 in hepatocellular carcinoma is associated with tumour proliferation, angiogenesis and Caspase-3 expression

Abstract

Aims: Unlike 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 vascularisation Methods and results: Immunohistochemistry 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. Conclusions:Our 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 TLR2 in HCC pathogenesis

Prognostic role of TLR4 and TLR2 in hepatocellular carcinoma

“…TLR2 expression in cytoplasm and cell nuclei have been previously reported [13]. TLR2 has been associated with grade of differentiation, stage and disease-free survival [6].…”

Single Nucleotide Polymorphisms from CSF2, FLT1, TFPI and TLR9 Genes Are Associated with Prelabor Rupture of Membranes

“…and M. hominis), Chlamydia trachomatis and/or the growth of any bacteria except coagulase-negative Staphylococcus epidermidis [12,32]. For TLR2, TLR4, TLR6 and TLR9 receptors, their participation in angiogenesis, one of the key processes involved in the development and function of the placenta, has also been confirmed [14,[33][34][35]. TLR2 has been demonstrated to induce the expression of the angiogenic factor angiopoietin 2 (ANGPT2), as well as the MMP2 and MMP9 proteins, involved in destabilization and development of blood vessels [36].…”

A multi‐omics‐based investigation of the immunological and prognostic impact of necroptosis‐related genes in patients with hepatocellular carcinoma

“…Alec E Vaezi et al 26 reported that PCYT1A (phosphate cytidylyltransferase 1A, choline) has biomarker value in patients with lung cancer and that high PCYT1A expression implies longer survival, but there is a lack of studies in hepatocellular carcinoma. The positive correlation between TLR2 (toll‐like receptor 2) expression and other proliferation and angiogenesis markers in hepatocellular carcinoma suggests a possible role for TLR2 in the pathogenesis of HCC 27 . PARP2 (poly(ADP‐ribose) polymerase 2) is associated with different functions of cells in the innate immune response 28 …”

“…The positive correlation between TLR2 (toll‐like receptor 2) expression and other proliferation and angiogenesis markers in hepatocellular carcinoma suggests a possible role for TLR2 in the pathogenesis of HCC. 27 PARP2 (poly(ADP‐ribose) polymerase 2) is associated with different functions of cells in the innate immune response. 28 …”