Abstract
CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes. The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells. Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies. However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded. In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies. We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection. These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
Highlights
Gastric cancer (GC) is one of the major problems in public health worldwide, killing up to nearly one million people worldwide each year [1]
In order to evaluate in vitro gastric cancer cell models displaying O-glycosylation features commonly observed in gastric tumors, previously generated genetic engineered models of
In the SC model, and since the STn expression is homogenous, we were not able to find differences between nondividing and dividing cells. These results demonstrate that the selected glycoengineered cell lines are good models to study O-glycan truncation in gastric cancer
Summary
Gastric cancer (GC) is one of the major problems in public health worldwide, killing up to nearly one million people worldwide each year [1]. Major efforts are focusing on targeting the cells with tumor-initiating capacities, cancer stem cells (CSCs), whose unlimited proliferation potentials are known to drive tumor growth, invasion, metastasis, and resistance to various forms of therapy [3,4]. Among the known CSCs biomarkers, CD44 has unique features that make it one of the most promising tumor markers. CD44 is a transmembrane glycoprotein broadly expressed among different cells and is known as the major receptor for hyaluronic acid (HA) [5]. Previous studies demonstrated that CD44-positive GC cells displayed all basic CSC features and chemo- and radio-resistance properties, which are likely to account for the resistance of this tumor type to most standard treatment protocols [6]
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