In situ expression of integrins in human hepatocellular carcinoma

Abstract

Integrins are plasma membrane integral proteins, composed of α and β subunits and distributed on various normal and neoplastic cells. They serve a function as cellular receptors for extracellular matrix proteins. In order to reveal the distinct distribution of integrins on hepatocellular carcinoma (HCC) cells, we studied for the expression of α2, α3, α4, α5, α6, αv, β1, β3, and β4 integrin subunits in 12 HCC and adjacent inflamed liver, and three normal liver tissues, using monoclonal antibodies against each subunit by indirect immunoperoxidase method. The expression of α2 subunit in cytoplasm, and that of α6, β1, and β3 subunits mainly on cell membrane was constantly observed in HCC cells. The α6 subunit showed remarkable de novo expression on all HCC cells without any relation to their differentiation grade, but not on hepatocytes in inflamed liver except for severe inflamed and fibrotic lesions. Others showed no difference in expression patterns between HCC cells and hepatocytes. α3, α4, αv, and β4 subunits were absent from HCC cells and inflamed hepatocytes, and the α5 subunit was weakly stained on them. In the normal liver tissues, the expression of all integrin subunits examined was almost negative or faint on hepatocytes. We conclude that the strong de novo expression of α6 integrin subunit is the most conspicuous feature of HCC cells, when compared with normal and inflamed hepatocytes, and that it is a possible immunocytochemical marker of HCC cells to distinguish them from non-neoplastic hepatocytes.