Journal
BIOCHEMICAL PHARMACOLOGY
Volume 168, Issue -, Pages 108-118Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2019.06.020
Keywords
Glypicans; Cancer; Cell signaling; Tumor microenvironment; Drug development
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Funding
- Department of Defense Prostate Cancer Research Program Idea Development Award [PC150431 GRANT11996600]
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Glypicans are evolutionary conserved, cell surface heparan sulfate (HS) proteoglycans that are attached to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. Glypicans interact with a broad class of soluble and insoluble ligands, such as morphogens, growth factors, chemokines, receptors and components of the extracellular matrix (ECM). Such versatility comes from their ability to interact through both their HS chains and core protein. Glypicans are involved in cellular and tissue development, morphogenesis and cell motility. They exhibit differential expression in several cancers, acting as both tumor promoters and inhibitors in a cancer type-specific manner. They also influence tumor stroma by facilitating angiogenesis, ECM remodeling and alteration of immune cell functions. Glypicans have emerged as a new therapeutic moiety, whose functions can be exploited in the field of targeted therapies and precision medicine in cancer. This is demonstrated by the emergence of several anti-glypican antibody-based immunologics that have been recently developed and are being evaluated in clinical trials. This review will focus on glypican structure and function with an emphasis on their expression in various cancers. Discussion will also center on the potential of glypicans to be therapeutic targets for inhibition of cancer cell growth.
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