Extracellular Galectin-3/Carbohydrate Interactions Modulate Cancer Cellular Migration

Galectin-3-mediated processes are important during many aspects of cancer progression, but they are not well understood. Galectin-3 is present extracellularly, and because of its carbohydrate recognition domain (CRD) and unstructured N-terminal domain (NTD), galectin-3 undergoes multimerization, which influences events such as carbohydrate-controlled cell–cell interactions. Investigations reported herein using an in vitro wound-healing assay show that exogenous galectin-3 inhibits cancer cellular migration. Since the addition of the galectin-3 CRD without the NTD does not arrest cellular migration, we attribute the effect of full-length galectin-3 on migration to the extracellular interactions between multimeric, full-length galectin-3 and extracellular receptors. In this publication, lactose-functionalized dendrimers serve as multivalent binding partners for galectin-3 and are used to mitigate extracellular multivalent galectin/carbohydrate interactions. The addition of lactose-functionalized dendrimers provides significant restoration of cellular migration in the presence of exogenous galectin-3 without increasing cellular viability. Thus, although galectin-3/protein interactions within the cell are known to increase both cellular migration and viability, cell surface galectin-3/carbohydrate interactions have the opposite impact and decrease cellular migration.