Abstract
Glycans are important partners in many biological processes, including carcinogenesis. The rapidly developing field of functional glycomics becomes one of the frontiers of biology and biomedicine. Aberrant glycosylation of proteins and lipids occurs commonly during malignant transformation and leads to the expression of specific tumor-associated glycans. The appearance of aberrant glycans on carcinoma cells is typically associated with grade, invasion, metastasis and overall poor prognosis. Cancer-associated carbohydrates are mostly located on the surface of cancer cells and are therefore potential diagnostic biomarkers. Currently, there is increasing interest in cancer-associated aberrant glycosylation, with growing numbers of characteristic cancer targets being detected every day. Breast and ovarian cancer are the most common and lethal malignancies in women, respectively, and potential glycan biomarkers hold promise for early detection and targeted therapies. However, the acceleration of research and comprehensive multi-target investigation of cancer-specific glycans could only be successfully achieved with the help of a combination of novel high-throughput glycomic approaches.
Highlights
In this review, we provide an overview of well described tumor-associated glycans in gynecological cancers, in ovarian and breast cancers, as the most common and lethal cancers in women, respectively
An extensive study performed in patients with gastric, colon, rectal and breast cancer revealed that anti-tumor-associated carbohydrate antigens (TACA) antibodies of IgM subclass against five known cancer antigens bind to carbohydrates on tumor-specific receptors and contribute to apoptosis, possibly playing an immuno-surveillance role [29]
Using the same monoclonal antibodies (mAb) directed to sTn, another study found detectable levels of sTn in serum of ovarian cancer patients which significantly correlated with increased malignancy, metastatic progression and low patient survival [100]
Summary
We provide an overview of well described tumor-associated glycans in gynecological cancers, in ovarian and breast cancers, as the most common and lethal cancers in women, respectively. We link tumor associated carbohydrates (TAC) to antigenicity and its recognition by the immune system via detection of naturally occurring anti-glycan antibodies. Most of these findings were based on classical studies, such as immunohistochemical staining and ELISA, but with the recent development of glycomic microarray platforms, such as printed glycan array (PGA), glycopeptide array, surface plasmon resonance (SPR) array, suspension array and others, this research has grown rapidly. The possible biochemical mechanisms of action of cancer-associated glycans in cancer 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
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