INHIBITION OF LECTIN MEDIATED OVARIAN TUMOR-CELL ADHESION BY SUGAR ANALOGS

Adhesion of A-121 human ovarian carcinoma cells to extracellular matri x is partly mediated via interaction between galaptin, an endogenous b eta-galactoside-binding lectin present in extracellular matrix, and sp ecific cell surface carbohydrate receptors identified as lysosomal ass ociated membrane proteins, lamp-1 and lamp-2. In this study, we report that adhesion of human ovarian carcinoma cells to polystyrene plates coated with polymerized human splenic galaptin can be inhibited by pol yclonal antibodies raised against lamp-1 and lamp-2 molecules and by p retreatment of A-121 human ovarian carcinoma cells with glucosamine an alogs: ri-O-acetyl-3-deoxy-3-fluoro-alpha-D-glucopyranose (3-F-GlcNAc) and ri-O-acetyl-4-deoxy-4-fluoro-alpha-D-glucopyranose (4-F-GlcNAc). A 48-h exposure of A-121 cells to individual sugar analogs, or to a co mbination of the two, resulted in a concentration-dependent inhibition of cellular attachment to polymerized galaptin. Both drugs inhibited glycoprotein biosynthesis as measured by cellular incorporation of lab eled [H-3]glucosamine and [H-3]fucose with negligible effects on [H-3] thymidine and [H-3]leucine incorporation and cell growth. As a result of drug action on glycoprotein biosynthesis, an alteration in the stru cture of the galaptin receptor was noted by indirect immunofluorescenc e and Western blot analysis. Moreover, probing gels of cell extracts w ith anti-lamp antibodies or Datura stramonium lectin demonstrated sign ificant changes in the reactivity and pattern of glycoprotein staining , suggesting an effect of sugar analogs on the glycosylation of variou s cellular receptor molecules. The greatest change was observed when t umor cells were exposed to a combination of the two sugar analogs. The se studies suggest that specific endogenous lectins and their surface receptors play a role in tumor cell adhesion and perhaps metastasis an d may serve as suitable targets for therapeutic exploitation.