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Abstract

The present invention provides antagonists to cell adhesion useful in controlling the negative effects of inflammation, and the metastasis of cancer cells. These antagonists are ligands to E-selectin containing the sialyl Le.sup.x structure, including sialyl Le.sup.x glycoproteins, sialyl Le.sup.x glycolipids, and sialyl Le.sup.x oligsaccharides, and other related sialyl Le.sup.x -containing molecules capable of inhibiting E-selectin mediated cell adhesion to endothelial cells. The present invention also provides antibodies against sialyl Le.sup.x determinants capable of interrupting E-selectin mediated cell adhesion, which are also considered antagonists according to the present invention. The present invention also provides methods of using the antagonists of the present invention to reduce inflammation, and methods to inhibit the process of metastasis by carcinogenic cells. The present invention also provides nucleic acid molecules encoding the glycoprotein antagonists of the present invention, in particular soluble chimeric leukosialin, and vectors capable of expressing these nucleic acid molecules, as well as cells capable of producing sialyl Le.sup.x positive recombinant glycoproteins. The present invention further provides a method of determining metastatic potential by comparing the efficiency of E-selectin-mediated adhesion of cell samples. In addition the present invention provides a method of producing a preferred antagonist of the present invention, sialyl Le.sup.x positive glycoproteins, in particular, sialy Le.sup.x positive chimeric leukosialin.

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First Claim