Adhesion of Tumor Cells to Hepatocytes: Different Mechanisms for Mammary Carcinoma Compared With Lymphosarcoma Cells

Abstract

Mechanisms of adhesion between tumor cells and hepatocytes, which are likely to play a role in liver metastasis formation, were studied in vitro. TA3 mammary carcinoma and MB6A lymphosarcoma cells were added to rat hepatocytes that had been cultured for 24 hours. Adhesion was quantified by counting adherent cells seen in sections of pelleted, Epon-embedded culture fragments. Adhesion of TA3, but not of MB6A cells, was inhibited by antibodies prepared from an antiserum raised against sinusoidal face-enriched liver plasma membranes. Detergent-solubilized liver components, affinity purified on immobilized inhibitory antibodies, neutralized inhibition, whereas a subfraction separated from this material with the use of immobilized noninhibitory antiliver antibodies had no neutralizing activity. Adhesion of MB6A but not of TA3 cells was inhibited by the calcium ionophore A23187 and the local anesthetic procaine. The calmodulin inhibitor trifluoperazine inhibited adhesion of MB6A cells more strongly than that of TA3 cells. Finally, adhesion of TA3 cells was dependent on external calcium, whereas in the case of MB6A cells calcium could be replaced by magnesium. These observations suggested that adhesion of the two tumor cell types to hepatocytes involved distinct hepatocyte surface molecules and required distinct biochemical machinery.