Tight junction proteins in HCC and metastatic liver tumours

Introduction/Aim. Cell adhesion has an important role in tumour progression. Tight junctions (TJ) have already been implicated in carcinogenesis. The 3 main integral membrane constituents, claudins, occludin and junctional adhesion molecule (JAM) participate in the regulatation of paracellular permeability and solute transport. We have investigated claudin expression in liver malignancies formerly. Now the expression of occludin, JAM-1,-2,-3 and the scaffolding protein zonula occludens (ZO)-1,-2,-3 was analysed. Materials and methods. 15 human hepatocellular carcinoma (HCC) and 15 liver metastasis of colon cancer cases were studied. Gene expression levels were determined with relative quantification to housekeeping genes by real-time PCR. Protein localisation was detected by immunohistochemistry comparing tumours to surrounding parenchyma and to normal liver samples (7). Results. ZO-2, JAM-2 and occludin mRNAs were significantly downregulated in HCC compared to normal liver (15.3x, 5.9x and 8.2x) and to surrounding tissues (3.4x, 3.2x and 2.2x). In metastasis ZO-2, JAM-2 and occludin were downregulated (9.6x, 18.6x, 12.1x) with respect to normal liver. Altered protein expression in tumours confirmed mRNA data. Discussion. TJ components' expression decreases in concordance with diminishing cell adhesion in tumours, however TJs constituents have not only a quantitative but also a qualitative alteration. The ratio of TJ proteins changes, what can mean also a diverse regulation or loss of selective permeability. TJ profile of primary and secondary tumours show different characteristics, which might refer to differences in their biological properties. The project was supported by grants: Bio14/2001, NKFP-1/0023/2002, ETT- 228/201, OTKA-037838.