Protein (
lectin)-
carbohydrate (cellular
glycoconjugate) recognition is operative in biochemical information transfer.
Galectins constitute a family of endogenous galactoside-binding
lectins with conserved features in the binding site. The members of this
lectin category are assumed to be involved in cell adhesion and growth regulation. To assess to what extent the different modes of binding-site presentation and/or
carbohydrate fine-specificities will affect aspects of
galectin behavior, homodimeric cross-linking
galectin-1 and monomeric chimeric
galectin-3, with its
collagenase-sensitive stalk linked to the
carbohydrate-recognition domain, were investigated. Cell-surface expression of the two
galectins and accessible
galectin-binding sites on various tumor cell lines was ascertained by FACScan analysis. In particular,
ligand accessibility for the two
galectins differed for the tested cell line types. Binding of
tumor cells to
laminin and plasma or placental
fibronectin was generally reduced by treatment of cells or matrix with
galectins.
Galectin-3 was more efficient than
galectin 1 at impairing
laminin's potency as matrix. Cell binding of
galectin-1, on the other hand, proved on average more effective for blocking cell association to
fibronectins after its preincubation with cell
suspensions. Differences were also apparent in the biodistribution of the
galectins, where an avian homolog of
galectin- served as the control to distinguish effects of spatial and
sugar-binding features. Histopathological analysis of lymph-node-negative and -positive breast and
colorectal carcinomas (n = 180 including 60 metastatic lesions) indicated a correlation of either increased
galectin-1 binding and reduced
galectin-3 expression or reduced binding of both
galectins with the occurrence of lymph node lesions. Together with data on the
heparin-binding lectin, revealing reduced expression to be associated with a positive lymph-node status in the
breast cancer group, these results can be interpreted to reflect cell-type-dependent requirements of
galectin ligand presentation during the metastatic cascade. By introducing mammalian
lectins to
lectin-histochemical studies, the detection of quantitative differences in glycosylation brings an understanding of its cell
biological significance one step closer.