Modified heparan sulfate proteoglycans (HSPGs) (HSPG)

Modified heparan sulfate proteoglycans (HSPGs) are a specialized class of cell-surface glycoproteins that play a critical role in the tumor microenvironment [1, 3]. HSPGs consist of a core protein, such as syndecan or glypican, covalently linked to heparan sulfate glycosaminoglycan chains [13]. In solid tumors, these molecules undergo specific structural modifications, including changes in sulfation patterns (e.g., N-sulfation and 6-O-sulfation) and cleavage by enzymes like heparanase and sulfatases [1, 14]. These modifications enhance the ability of HSPGs to act as co-receptors for oncogenic growth factors like FGF, Wnt, and VEGF, thereby promoting tumor proliferation, angiogenesis, and metastasis [3, 7]. Interestingly, these tumor-specific modifications also create unique binding sites for certain viruses, such as the Human Papillomavirus (HPV) [2, 12]. This unique tropism is exploited by novel therapeutic platforms, such as virus-like drug conjugates (VDCs), which use HPV-derived particles to selectively deliver cytotoxic payloads to cancer cells while sparing healthy tissue [5, 9]. By targeting the unique 'sugar code' of the tumor surface, these therapies aim to achieve high precision in treating various solid tumors, including choroidal melanoma and bladder cancer [10, 14].

Other names

Tumor-associated heparan sulfate proteoglycansSpecifically modified HSPGsHPV-binding heparan sulfate proteoglycansSulfated glycosaminoglycansModified heparan sulfate proteoglycans on solid tumor cell surfaces

Selective binding of virus-like particles to modified heparan sulfate chains followed by light-induced cytotoxicity; Inhibition of heparanase and sulfatase enzymes; Competitive inhibition of growth factor binding to heparan sulfate