Our long range goals are to understand the molecular mechanisms underlying cell-cell recognition and specific intercellular adhesion and to determine how these processes affect normal and abnormal development, malignancy, and metastasis. We have shown that specific intercellular adhesion is a complex, multi-step, energy- requiring process that must involve the rapid mobilization of different kinds of molecules. Assays have been devised to follow the adhesion process kinetically, and with these assays we measure the effects of exogenous factors on the rate. Adhesive specificity is essential for in vitro studies, and two systems have been developed that exhibit the required specificities, i.e., hepatocytes from young rats and chickens, and the corresponding liver plasma membranes. The membranes are the starting point for the isolation of """"""""specific adhesive factors"""""""". The rate-limiting factor in chicken liver plasma membranes, CHAG, has been detected in Ca2+-free perfusates of the liver (where the cells virtually separate from one another), and has been purified to apparent homogeneity from liver homogenates. CHAG is a unique ganglioside that occurs in trace quantities in chicken liver, and is recognized by intact chicken but not rat hepatocytes. The specific CHAG receptor will be purified by affinity chromatography. Rat liver contains a similar ganglioside(s) that have been partially purified, and that are recognized by rat hepatocytes. A different adhesion factor, a glycoprotein, has also been purified from rat liver plasma membranes. Immediate goals are to completely characterize the ganglioside and glycoprotein adhesion factors, to isolate their respective receptors, and to determine how these glycolipids and proteins function in the over-all process. The occurrence and distribution of each of these components will then be determined in normal liver, hepatocytes in vitro as they form trabeculae, embryonic, regenerating, and pathological livers and hepatomas.
