The long-range goals of this project are to define the biochemical events involved in cell-cell recognition and adhesion and to determine how these processes affect normal and abnormal development, malignancy, and metastasis. Immediate specific aims are: (1) to continue present studies on the purification of specific adhesive factors in the liver plasma membranes of chicken and rats. These factors specifically stimulate the homologous hepatocytes to adhere to a more rapid rate. The factor from chicken liver membranes, CF, has been extensively purified and appears to be an O-acylated highly polar ganglioside. All activity is lost when CF is treated with either sialidase or with dilute alkali at room temperature. The rat liver factor, RF, has also been purified about 5,000-fold and appears to be a glycoprotein with unusual physical properties; (2) to attempt to identify and isolate complementary molecules on hepatocyte cell surfaces that recognize and bind to RF and CF; (3) following isolation of RF and CF in homogenous form, to prepare monoclonal antibodies against the factors to be used to determine the quantity of each of these components in hepatocytes from normal, embryonic, and regenerating liver, as well as subcellular localization. Extensive studies will also be performed on the hepatocarcinomas (rat) to determine whether RF has changed qualitatively or quantitatively in such tumors, particularly in their highly metastatic variants; (4) to continue model studies on cell adhesion, whereby ligands from monosaccharides through glycoproteins will be covalently linked to nonadherent surfaces such as polyacrylamide, and the interactions between these covalent derivatives and intact cells will be studied. Present work with Dictyostelium discoideum along these lines will be continued; and (5) the long-term effects of glycoses (glycopeptides, glycoproteins, etc.) on cell morphology, motility, growth, etc., will be studied using a similar approach but where the ligands are covalently linked to a copolymer of polystyrene. (V)
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