Altered Sialylation and Sialyltransferase Expression in Gynecologic Cancers

Abstract

Sialic acids and their derivatives are ubiquitous at the terminal positions of the oligosaccharides of glycoproteins that play roles in a variety of biologic processes, such as cell-cell communication, cell-matrix interaction, adhesion, and protein targeting. Altered sialyltransferase (ST) expression plays an important role in oncogenesis, tumor progression, and lymph node metastases. For example, in squamous cell carcinoma of the cervix, α2,6-ST I shows positive correlation not only with oncogenesis, but also with tumor metastases to the pelvic lymph node. The over-expression of α2,6-ST I is due to reactivation of the hepatic form of the promoter. With advanced metastases, α2,3-linkage also dramatically changes, and this change more accurately predicts pelvic lymph node metastases in squamous cell carcinoma of the cervix. This laboratory successfully cloned α2,3-, α2,6-, and α2,8-ST genes to screen a powerful anti-ST reagent, soyasaponin I (SsaI). SsaI is not cytocidal but, in contrast, has a cytostatic effect on cancer cells, mainly slowing cell growth and division. It also modifies the invasive behavior of cancer cells such as migration and adhesion. Thus, altered glycosylation is important in gynecologic cancers, especially squamous cell carcinoma of the cervix. In future, the functional roles of ST in cancer pathogenesis may be elucidated. For example, specific anti-ST inhibitors could clarify the role of changing sialylation in cancer behavior, monoclonal antibodies to certain glycosylated epitopes will help diagnosis of such tumors and, most importantly, both these techniques will offer therapeutic avenues designed to attack tumor cells via their glycans in the near future.

Keywords

• neoplasms of the cervix
• prognosis
• sialic acid
• sialyltransferase