Circulating Proteoglycans/Glycosaminoglycans as Cancer Biomarkers

Cancer propagation and progression are associated with remarkable remodeling of the extracellular microenvironment with the formation of a permissive matrix for tumor growth, enriched in inflammatory mediators and matrix-degrading enzymes. Proteoglycans, which represent major structural and functional extracellular matrix components, play pivotal roles by affecting tissue organization, cell–matrix interactions, cell signaling, and, ultimately, cell behavior in physiological conditions as well as during cancer development and progression. In this respect, the proteolytic activity in tumor stroma liberates bioactive fragments, which can be detected in serum and may be useful as diagnostic and prognostic markers. Furthermore, since cell surface proteoglycans are specifically expressed by cancer cells, as in the case of glypican-3 in hepatocellular carcinoma, they can represent potential promising targets for immunotherapy. This chapter reviews and critically addresses the major clinical literature and provides an overview of the significance of circulating proteoglycans (PGs) and glycosaminoglycans (GAGs), especially their soluble forms originating from the cell surface heparan sulfate proteoglycans syndecans and glypicans, in both prognosis and diagnosis of various malignancies responsible for high mortality and disability, including hepatocellular carcinoma, multiple myeloma, breast cancer, and renal cell carcinoma. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.