THE MUCIN EPIGLYCANIN ON TA3 HA CARCINOMA-CELLS PREVENTS ALPHA(6)BETA(4)-MEDIATED ADHESION TO LAMININ AND KALININ AND E-CADHERIN-MEDIATED CELL-CELL INTERACTION/

TA3/Ha murine mammary carcinoma cells grow in suspension, do not adher e to extracellular matrix molecules, but do adhere to hepatocytes and form liver metastases upon intraportal injection. Recently we showed t hat the integrin alpha(6) beta(4) on the TA3/Ha cells is involved in a dhesion to hepatocytes. However, despite high cell surface levels of a lpha(6) beta(4), TA3/Ha cells do not adhere to the alpha(6) beta(4) li gands laminin and kalinin. Here we show that this is due to the mucin epiglycanin that is highly expressed on TA3/Ha cells. Some monoclonal antibodies generated against epiglycanin induced capping of most of th e epiglycanin molecules. TA3/Ha cells treated with these mAb did adher e to laminin and kalinin, and an epithelial monolayer was formed on ka linin, with alpha(6) beta(4) localized in HD1-containing hemidesmosome -like structures and E-cadherin at the cell-cell contact sites. Simila r results were obtained after treatment of TA3/Ha cells with O-sialogl ycoprotein endopeptidase which removes all epiglycanin. In addition, t he enzyme induced E-cadherin-mediated cell-cell aggregation. Both trea tments also enhanced the adhesion to hepatocytes, but given the potent antiadhesive effect of epiglycanin it is remarkable that nontreated T A3/Ha cells adhere to hepatocytes at all. We found that during this in teraction, epiglycanin was redistributed. We conclude that epiglycanin can completely prevent both intercellular and matrix adhesion, but th at this effect can be overcome in certain intercellular interactions b ecause of the induced redistribution of the mucin.