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

12 Citations (Scopus)

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

Fingerprint

Heparan Sulfate Proteoglycans
Sarcoma
Proteoglycans
Therapeutics
Syndecans
Glypicans
Cellular Microenvironment
Neoplasms
Disease Management
heparanase
Clinical Trials
Growth

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The heparanase/heparan sulfate proteoglycan axis : A potential new therapeutic target in sarcomas. / Cassinelli, Giuliana; Zaffaroni, Nadia; Lanzi, Cinzia.

In: Cancer Letters, Vol. 382, No. 2, 28.11.2016, p. 245-254.

Research output: Contribution to journalShort survey

@article{56c9e04f66e448eeb193301f9a2ad445,
title = "The heparanase/heparan sulfate proteoglycan axis: A potential new therapeutic target in sarcomas",
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.",
keywords = "Heparan sulfate mimetic, Heparan sulfate proteoglycan, Heparanase, Heparanase inhibitor, Sarcoma",
author = "Giuliana Cassinelli and Nadia Zaffaroni and Cinzia Lanzi",
year = "2016",
month = "11",
day = "28",
doi = "10.1016/j.canlet.2016.09.004",
language = "English",
volume = "382",
pages = "245--254",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - The heparanase/heparan sulfate proteoglycan axis

T2 - A potential new therapeutic target in sarcomas

AU - Cassinelli, Giuliana

AU - Zaffaroni, Nadia

AU - Lanzi, Cinzia

PY - 2016/11/28

Y1 - 2016/11/28

N2 - 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.

AB - 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.

KW - Heparan sulfate mimetic

KW - Heparan sulfate proteoglycan

KW - Heparanase

KW - Heparanase inhibitor

KW - Sarcoma

UR - http://www.scopus.com/inward/record.url?scp=84989307739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989307739&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2016.09.004

DO - 10.1016/j.canlet.2016.09.004

M3 - Short survey

VL - 382

SP - 245

EP - 254

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 2

ER -