Abstract
Cancer is a malignant tumor that threatens the health of human beings, and has become the leading cause of death in urban and rural residents in China. The glycocalyx is a layer of multifunctional glycans that covers the surfaces of a variety of cells, including vascular endothelial cells, smooth muscle cells, stem cells, epithelial, osteocytes, as well as cancer cells. The glycosylation and syndecan of cancer cell glycocalyx are unique. However, heparan sulfate (HS), hyaluronic acid (HA), and syndecan are all closely associated with the processes of cancer progression, including cell migration and metastasis, tumor cell adhesion, tumorigenesis, and tumor growth. The possible underlying mechanisms may be the interruption of its barrier function, its radical role in growth factor storage, signaling, and mechanotransduction. In the later sections, we discuss glycocalyx targeting therapeutic approaches reported in animal and clinical experiments. The study concludes that cancer cells’ glycocalyx and its role in cancer progression are beginning to be known by more groups, and future studies should pay more attention to its mechanotransduction of interstitial flow-induced shear stress, seeking promising therapeutic targets with less toxicity but more specificity.
Highlights
Introduction and overviewThe glycocalyx is a surface layer that covers multiple cells and is mainly composed of proteoglycans and glycoproteins
Afratis et al [62] demonstrated that syndecans and glypicans can accelerate cell signaling, focal adhesion kinase phosphorylation, tumor growth and migration
Studies have shown that humanized GC33, a humanized anti-GPC3 monoclonal antibody significantly inhibits the growth of GPC3-positive human hepatocellular carcinoma (HCC) xenografts in SCID mice; the mechanism induces antibody-dependent cellular cytotoxicity (ADCC) [151]
Summary
The glycocalyx is a surface layer that covers multiple cells (i.e., endothelial cells, smooth muscle cells, stem cells, and cancer cells, among others) and is mainly composed of proteoglycans and glycoproteins. The composition, physiology, and pathology of vascular cell glycocalyx have been sophisticatedly reviewed in several published papers. We attempt to elucidate knowledge about cancer cell-specific glycocalyx: Its altered glycosylation and syndecan expression. Principle emphasis is on the effects of different components of the glycocalyx (heparan sulfate, hyaluronic acid, syndecans) on the progression of cancer, including the convenience of cancer cell migration and metastasis, cancer cell adhesion, tumorigenesis and tumor growth. We discuss the possible mechanisms of glycocalyx involved in cancer progression and collate glycocalyx-specific targeting therapeutic approaches that have been reported up to now
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