Tumor cell surface glycans and heparan sulfate proteoglycans (HSPGs)

Tumor cell surface glycans and heparan sulfate proteoglycans (HSPGs) are critical components of the tumor glycocalyx, a carbohydrate-rich layer that mediates interactions between cancer cells and their microenvironment (Fuster & Esko, 2005; https://doi.org/10.1038/nrc1649). HSPGs, such as syndecans and glypicans, consist of core proteins with attached heparan sulfate chains that function as co-receptors for various growth factors, including FGF and VEGF, thereby promoting tumor growth and angiogenesis (Knelson et al., 2014; https://doi.org/10.1038/nrc3787). In many cancers, the expression of these molecules is dysregulated, and the enzyme heparanase is often overexpressed to remodel the extracellular matrix and release sequestered signaling molecules (Hammond et al., 2014; https://doi.org/10.1093/glycob/cwu003). Therapeutic strategies targeting this system include heparin mimetics like muparfostat and roneparstat, which inhibit heparanase and sequester growth factors to prevent signaling. Additionally, specific proteoglycans like Glypican-3 (GPC3) and Syndecan-1 (CD138) are targeted by monoclonal antibodies and CAR-T cell therapies to achieve tumor-specific cytotoxicity. However, the development of these therapies is complicated by the structural heterogeneity of glycans and the potential for off-target effects on the normal vasculature and coagulation system.

Other names

Tumor glycocalyxCell surface glycosaminoglycansCancer-associated glycansHSPGs

Inhibition of heparanase enzyme activity, competitive sequestration of heparin-binding growth factors (e.g., VEGF, FGF), and direct targeting of proteoglycan core proteins via monoclonal antibodies or CAR-T cells to induce cell death.