Effect of the hepatitis B virus HBx protein on integrin-mediated adhesion to and migration on extracellular matrix

Background/Aims: The hepatitis B virus HBx protein is associated with the d evelopment of hepatocellular carcinoma (BCC), However, its possible contrib ution to tumor spreading has not been explored. The migration of tumor cell s through the extracellular matrix (ECM) represents a crucial step in tumor metastasis, Our aim was to study the effect of HBx on the integrin-mediate d cell-ECM interaction, and its possible consequences for cell migration. Methods: Cell-ECM interaction was evaluated by static adhesion experiments, using blocking and stimulating anti-beta1 integrin mAbs, ECM receptor expr ession was analyzed by flow cytometry, The cellular distribution of the act ivated pi integrin subunit was determined by immunofluorescence analysis, a nd cell motility was determined by wound-healing assays. Results: HBx-bearing cells showed decreased adhesion to fibronectin, which correlated with a decreased expression of the alpha5 integrin subunit, The activated pi subunit was redistributed to the tips of pseudopodial protrusi ons of HBx-bearing cells, whereas it was evenly localized in the control ce lls. HBx-induced cell migration was abrogated by irreversible stimulation o f Pt integrins. Conclusions: These results suggest that HBx might play a role in tumor spre ading by modulating the adhesion-deadhesion balance of the cells in the pri mary tumor site and favoring integrin-mediated cell migration. (C) 2001 European Association for the Study of the Liver, Published by Else vier Science B,V, All rights reserved.