Mini-reviewThe heparanase/heparan sulfate proteoglycan axis: A potential new therapeutic target in sarcomas

- The heparanase/HSPG system is a critical player in tumor growth and progression.
- Heparanase expression is associated with aggressiveness and poor prognosis in various sarcomas.
- Expression of specific HSPGs is deregulated in specific sarcoma subtypes.
- Heparanase/HSPG-dependent signaling pathways are deregulated in sarcoma subtypes.
- The heparanase/HSPG axis represents an attractive therapeutic target in sarcomas.

Heparanase, the only known mammalian endoglycosidase degrading heparan sulfate (HS) chains of HS proteoglycans (HSPG), is a highly versatile protein affecting multiple events in tumor cells and their microenvironment. In several malignancies, deregulation of the heparanase/HSPG system has been implicated in tumor progression, hence representing a valuable therapeutic target. Currently, multiple agents interfering with the heparanase/HSPG axis are under clinical investigation. Sarcomas are characterized by a high biomolecular complexity and multiple levels of interconnection with microenvironment sustaining their growth and progression. The clinical management of advanced diseases remains a challenge. In several sarcoma subtypes, high levels of heparanase expression have been correlated with poor prognosis associated factors. On the other hand, expression of cell surface-associated HSPGs (i.e. glypicans and syndecans) has been found altered in specific sarcoma subtypes. Recent studies provided the preclinical proof-of-principle of the role of the heparanase/HSPG axis as therapeutic target in various sarcoma subtypes. Although currently there are no clinical trials evaluating agents targeting heparanase and/or HSPGs in sarcomas, we here provide arguments for this strategy as potentially able to implement the therapeutic options for sarcoma patients.