However, the possible biochemical mechanisms of action of cancer-associated glycans in cancer Selleck CYC202 progression are still under evaluation and are not part of this review, where we will focus more on their occurrence in gynecological cancers and their clinical relevance. 1.1. Glycans and Cancer Glycans (carbohydrates) are poly- or oligosaccharides, homo- or heteropolymers of monosaccharide residues, and important partners in many biological processes including Inhibitors,research,lifescience,medical carcinogenesis. Aberrant glycosylation of proteins and lipids occurs commonly during malignant transformation and leads to the expression of tumor-specific glycans [1,2].
The alterations in glycosylation develop very early during carcinogenesis, before any destructive changes in proliferation/apoptosis or cell differentiation Inhibitors,research,lifescience,medical become discernible [3]. Tumor-associated carbohydrates (TAC) are expressed by both tumor and host cells and are involved in the key pathophysiological processes during the various steps of tumor progression, including tumor growth, cell migration, invasion, metastasis, angiogenesis, and evasion of innate immunity Inhibitors,research,lifescience,medical [4,5,6,7,8,9]. In past three decades TAC were studied
extensively for the use as specific tumor biomarkers and potential therapeutic targets, however, their biological role and functional Inhibitors,research,lifescience,medical mechanisms remain still unknown. The classically known TAC are sialyl- Lewisa (sLea), T (or TF, Thomsen-Friedenreich) antigen and Thomsen-nouvelle antigen (Tn), an unsubstituted GalNAc. Basically, TAC can be divided into three major groups: (A) glycosphingolipids of the ganglio- and globo-series; (B) modified lacto-series type 1 (GalĪ²1-3GlcNAc) or type 2 chains (GalĪ²1-4GlcNAc), and (C) core glycan structures
of O-linked mucin type (T and Tn antigens) [10,11] (Figure 1). Figure 1 The major tumor-associated glycan determinants, reported to be involved in gynaecological Inhibitors,research,lifescience,medical cancers. Glycan structures were designed using GlycoWorkbench [18]. The appearance of aberrant glycan structures, characterized by truncations, increased branching, altered sialylation and/or fucosylation on cancerous cells is typically associated with clinicopathological characteristics such as grade, metastasis and poor prognosis overall. In contrast, some TAC show opposite effects suppressing invasiveness and metastatic Adenylyl cyclase potential [2,12]. These aberrantly expressed glycans may reflect alterations of the cognate glycosyltransferase and/or glycosidase network and, initially, dysregulation of the enzyme expression [13,14]. Patterns of glycosyltransferase activities in cancer cell lines indicated that various cancer cells express certain glycan epitopes which could have diagnostic values or serve as treatment targets [10,15].