Adhesion of
A-121 human ovarian
carcinoma cells to extracellular matrix is partly mediated via interaction between
galaptin, an endogenous
beta-galactoside-binding lectin present in extracellular matrix, and specific cell surface
carbohydrate receptors identified as
lysosomal associated 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 polyclonal
antibodies raised against lamp-1 and lamp-2 molecules and by pretreatment of
A-121 human ovarian
carcinoma cells with
glucosamine analogs: 2-acetamido-1,4,6-tri-O-acetyl-3- deoxy-3-fluoro-alpha-D-glucopyranose (3-F-GlcNAc) and
2-acetamido-1,3,6-tri-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 combination 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 labeled [3H]
glucosamine and [3H]
fucose with negligible effects on [3H]
thymidine and [3H]
leucine incorporation and cell growth. As a result of
drug action on
glycoprotein biosynthesis, an alteration in the structure of the
galaptin receptor was noted by indirect immunofluorescence and Western blot analysis. Moreover, probing
gels of
cell extracts with anti-lamp
antibodies or
Datura stramonium lectin demonstrated significant changes in the reactivity and pattern of
glycoprotein staining, suggesting an effect of
sugar analogs on the glycosylation of various cellular receptor molecules. The greatest change was observed when
tumor cells were exposed to a combination of the two
sugar analogs. These studies suggest that specific endogenous
lectins and their surface receptors play a role in
tumor cell adhesion and perhaps
metastasis and may serve as suitable targets for therapeutic exploitation.