The heparanase/heparan sulfate proteoglycan axis: A potential new therapeutic target in sarcomas

Giuliana Cassinelli, Nadia Zaffaroni, Cinzia Lanzi

Research output: Contribution to journalShort survey

Abstract

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.

Original languageEnglish
Pages (from-to)245-254
Number of pages10
JournalCancer Letters
Volume382
Issue number2
DOIs
Publication statusPublished - Nov 28 2016

Keywords

  • Heparan sulfate mimetic
  • Heparan sulfate proteoglycan
  • Heparanase
  • Heparanase inhibitor
  • Sarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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