Negative regulation of neuroblastoma cell growth by carbohydrate-dependentsurface binding of galectin-1 and functional divergence from galectin-3

The cell density-dependent growth inhibition of human SK-N-MC neuroblastoma cells is initiated by increased ganglioside sialidase activity leading to elevated cell surface presentation of ganglioside GM1, a ligand of galectin -1. We herein show that the extent of the cell surface expression of the ga lectin coincides with marked increases of the sialidase activity. Reverse t ranscriptase-polymerase chain reaction analysis excludes a regulation at th e transcriptional level. Exposure of cells to purified galectin-1 reveals i ts carbohydrate-dependent activity to reduce cell proliferation. Assays to detect DNA fragmentation biochemically and cytometrically and to block casp ases render it unlikely that galectin-1 acts as a classical proapoptotic fa ctor on these cells. Because the chimeric galectin-3 shares binding sites a nd binding parameters with galectin-1 for these cells, we tested whether th is galectin will elicit the same response as the homodimeric cross-linking galectin-1. Evidently, galectin-3 fails to affect cell growth by itself but interferes with galectin-1 upon coincubation. Its proteolytically truncate d variant, the C-terminal lectin domain with impaired capacity to form aggr egates when surface bound, has only weak binding properties. Thus, the way in which the galectin-1 interacts topologically with an apparently common s et of ligands relative to galectin-3 is crucial for eliciting post-binding events. We conclude that galectin-1 is a probable effector in the sialidase -dependent growth control in this system. Moreover, the experiments with ga lectin-3 reveal functional divergence, most probably based on different top ologies of presentation of homologous carbohydrate-binding sites.