Galectin-3C: Human Lectin for Treatment of Cancer

A summary is provided of the compelling data supporting galectin-3, as a target for cancer therapy, and for the clinical development of a truncated form of human galectin-3, termed galectin-3C, for cancer. Lacking the N-terminal domain of galectin-3 that facilitates its multimerization when bound to carbohydrate ligands, galectin-3C functions as an inhibitor of the galectin-3 crosslinking mediated by the N-terminal domain that can be induced by multivalent oligosaccharides and glycoconjugates intra- or extracellularly, on cell surfaces, or in extracellular matrices. Numerous studies show that galectin-3 plays a key role in tumorigenicity and metastasis and is a novel target for the development of cancer therapeutics. Data presented indicate that galectin-3C can be localized in a carbohydrate-dependent manner similar to most information reported regarding galectin-3. Exogenous galectin-3C facilitated anoikis in human breast cells, illustrating an effect it is expected to produce in vivo by reducing cell-cell or cell-ECM adhesion of metastatic cells. Based on the activity of galectin-3, we postulate that galectin-3C also inhibits the metastatic process by preventing integrin activation and focal adhesion turnover. The data described provide evidence of the important functions of galectin-3 in the processes of metastasis and tumorigenicity, and the potential therapeutic effect of inhibiting the activity of galectin-3 with galectin-3C. Galectin-3 has a complex, multi-faceted role that is critical in the relationship between the cells of various types of malignancies and the microenvironment, and further development of galectin-3C as a clinical candidate for cancer treatment is warranted.