Recent advances toward the development of inhibitors to attenuate tumor metastasis via the interruption of lectin-ligand interactions

Abstract

Aberrant glycosylation is a well-recognized phenomenon that occurs on the surface of tumor cells, and the overexpression of a number of ligands (such as TF, sialyl Tn, and sialyl Lewis X) has been correlated to a worse prognosis for the patient. These unique carbohydrate structures play an integral role in cell-cell communication and have also been associated with more metastatic cancer phenotypes, which can result from binding to lectins present on cell surfaces. The most well studied metastasis-associated lectins are the galectins and selectins, which have been correlated to adhesion, neoangiogenesis, and immune-cell evasion processes. In order to slow the rate of metastatic lesion formation, a number of approaches have been successfully developed which involve interfering with the tumor lectin-substrate binding event. Through the generation of inhibitors, or by attenuating lectin and/or carbohydrate expression, promising results have been observed both in vitro and in vivo. This article briefly summarizes the involvement of lectins in the metastatic process and also describes different approaches used to prevent these undesirable carbohydrate-lectin binding events, which should ultimately lead to improvement in current cancer therapies.

Keywords: Aberrant glycosylations; Cancer metastasis; Cancer therapies; Galectins; Inhibition; Lectins; Lectin–carbohydrate interactions; Selectins; Siglecs; Tumor-associated antigens.