Differential expression of extracellular matrix proteins and integrins in hepatocellular carcinoma and chronic liver disease.

Extracellular matrix (ECM) molecules play an important role in the orderly development, differentiation and function of tissues. The interaction of ECM with heterodimeric transmembrane glycoproteins called integrins is thought to be an important factor in cell-cell and cell-substrate adhesions in tumours, tumour invasion and metastases. PURPOSE: To investigate ECM and adhesion molecules in hepatocellular and breast carcinomas, chronic hepatitis and hepatic cirrhosis. MATERIALS AND METHODS: Frozen in liquid nitrogen and also paraffin-embedded biopsies from hepatocellular adenomas (3), well-differentiated (53) and poorly differentiated (19) hepatocellular carcinomas, lobular (3) and poorly differentiated (7) breast carcinomas, chronic hepatitis (10) and hepatic cirrhosis (10) were collected and investigated. Immunohistochemical techniques were applied for the detection of ECM molecules fibronectin, laminin, tenascin, vitronectin and integrins alpha 5 and beta 4. RESULTS: Poorer differentiation of the tumours was characterised by up-regulation of fibronectin, tenascin and vitronectin and downregulation of laminin and both integrins. These changes were observed in the interface between tumour and invaded tissues and within cancerous sinusoids. CONCLUSION: Increased expression of some ECM glycoproteins around tumour foci suggests a role in stimulating cancer cells or a host defence mechanism accompanied by desmoplastic response to them. Downregulation of laminin in poorly differentiated tumours identifying loss of basement membrane components and parallels quantitative changes in the expression of adhesion molecules in both hepatic and breast carcinomas. This may be an important step in enhancing local invasiveness of tumour cells, facilitating tumour spreading and biological malignancy.