Glycosylation in Cholangiocarcinoma Development and Metastasis: Diagnostic and Therapeutic Considerations

With advancing technology in glycobiology research over the past decade, there is now a large and ever-growing number of publications examining the biological and clinical significance of glycosylation in human diseases. In cholangiocarcinoma (CCA), various alterations of global glycosylation, both in core glycosylation of N-glycans and O-Glycans as well as in peripheral fucosylation and sialylation, have been identified. The aberrant glycosylation occurs in a large number of cellular glycoproteins, including secreted, membrane-bound, and nucleocytoplasmic proteins. Several aberrant expressed glycans and glycoconjugates are applicable as tumor markers for diagnosis and prognostic prediction of CCA. Moreover, some specific glycans appear to be associated with short survival of the CCA patients and played important roles in proliferation, migration, invasion, and chemoresistance of CCA cells. Suppression of glycosylation and glycan functions by specific siRNA, lectins, or inhibitors could significantly reduce the metastatic potential of CCA cells and enhance their chemosensitivity. These findings suggest the potential of targeting glycosylation for CCA treatment and will be discussed in this chapter.