Syndecans as modulators and potential pharmacological targets in cancer progression
Extracellular matrix (ECM) components form a dynamic network of key importance for cell function and properties. Key macromolecules in this interplay are syndecans (SDCs), a family of transmembrane heparan sulfate proteoglycans (HSPGs). Specifically, heparan sulfate (HS) chains with their different...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2014-02-01
|
Series: | Frontiers in Oncology |
Subjects: | |
Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00004/full |
id |
doaj-3969222b3bac41a9b864d902713f4bce |
---|---|
record_format |
Article |
spelling |
doaj-3969222b3bac41a9b864d902713f4bce2020-11-24T23:54:16ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2014-02-01410.3389/fonc.2014.0000474118Syndecans as modulators and potential pharmacological targets in cancer progressionDespoina eBarbouri0Nikolaos eAfratis1Chrisostomi eGialeli2Demitrios H Vynios3Achilleas D Theocharis4Nikos eKaramanos5University of PatrasUniversity of PatrasUniversity of PatrasUniversity of PatrasUniversity of PatrasUniversity of PatrasExtracellular matrix (ECM) components form a dynamic network of key importance for cell function and properties. Key macromolecules in this interplay are syndecans (SDCs), a family of transmembrane heparan sulfate proteoglycans (HSPGs). Specifically, heparan sulfate (HS) chains with their different sulfation pattern have the ability to interact with growth factors and their receptors in tumor microenvironment, promoting the activation of different signaling cascades that regulate tumor cell behavior. The affinity of HS chains with ligands is altered during malignant conditions because of the modification of chain sequence/sulfation pattern. Furthermore, matrix degradation enzymes derived from the tumor itself or the tumor microenvironment, like heparanase and matrix metalloproteinases (MMPs), ADAM as well as ADΑMTS are involved in the cleavage of SDCs ectodomain at the HS and protein core level, respectively. Such released soluble syndecans shed syndecans in the extracellular matrix interact in an autocrine or paracrine manner with the tumor or/and stromal cells. Shed syndecans, upon binding to several matrix effectors, such as growth factors, chemokines and cytokines, have the ability to act as competitive inhibitors for membrane PGs, and modulate the inflammatory microenvironment of cancer cells. It is notable that syndecans and their soluble counterparts may affect either the behavior of cancer cells and/or their microenvironment during cancer progression. The importance of these molecules has been highlighted since HSPGs have been proposed as prognostic markers of solid tumors and hematopoietic malignancies. Going a step further down the line, the multi-actions of syndecans in many levels make them appealing as potential pharmacological targets, either by targeting directly the tumor or indirectly the adjacent stroma.http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00004/fullProteoglycansSyndecansTumor MicroenvironmentCancerHeparan sulfateshed syndecans |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Despoina eBarbouri Nikolaos eAfratis Chrisostomi eGialeli Demitrios H Vynios Achilleas D Theocharis Nikos eKaramanos |
spellingShingle |
Despoina eBarbouri Nikolaos eAfratis Chrisostomi eGialeli Demitrios H Vynios Achilleas D Theocharis Nikos eKaramanos Syndecans as modulators and potential pharmacological targets in cancer progression Frontiers in Oncology Proteoglycans Syndecans Tumor Microenvironment Cancer Heparan sulfate shed syndecans |
author_facet |
Despoina eBarbouri Nikolaos eAfratis Chrisostomi eGialeli Demitrios H Vynios Achilleas D Theocharis Nikos eKaramanos |
author_sort |
Despoina eBarbouri |
title |
Syndecans as modulators and potential pharmacological targets in cancer progression |
title_short |
Syndecans as modulators and potential pharmacological targets in cancer progression |
title_full |
Syndecans as modulators and potential pharmacological targets in cancer progression |
title_fullStr |
Syndecans as modulators and potential pharmacological targets in cancer progression |
title_full_unstemmed |
Syndecans as modulators and potential pharmacological targets in cancer progression |
title_sort |
syndecans as modulators and potential pharmacological targets in cancer progression |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2014-02-01 |
description |
Extracellular matrix (ECM) components form a dynamic network of key importance for cell function and properties. Key macromolecules in this interplay are syndecans (SDCs), a family of transmembrane heparan sulfate proteoglycans (HSPGs). Specifically, heparan sulfate (HS) chains with their different sulfation pattern have the ability to interact with growth factors and their receptors in tumor microenvironment, promoting the activation of different signaling cascades that regulate tumor cell behavior. The affinity of HS chains with ligands is altered during malignant conditions because of the modification of chain sequence/sulfation pattern. Furthermore, matrix degradation enzymes derived from the tumor itself or the tumor microenvironment, like heparanase and matrix metalloproteinases (MMPs), ADAM as well as ADΑMTS are involved in the cleavage of SDCs ectodomain at the HS and protein core level, respectively. Such released soluble syndecans shed syndecans in the extracellular matrix interact in an autocrine or paracrine manner with the tumor or/and stromal cells. Shed syndecans, upon binding to several matrix effectors, such as growth factors, chemokines and cytokines, have the ability to act as competitive inhibitors for membrane PGs, and modulate the inflammatory microenvironment of cancer cells. It is notable that syndecans and their soluble counterparts may affect either the behavior of cancer cells and/or their microenvironment during cancer progression. The importance of these molecules has been highlighted since HSPGs have been proposed as prognostic markers of solid tumors and hematopoietic malignancies. Going a step further down the line, the multi-actions of syndecans in many levels make them appealing as potential pharmacological targets, either by targeting directly the tumor or indirectly the adjacent stroma. |
topic |
Proteoglycans Syndecans Tumor Microenvironment Cancer Heparan sulfate shed syndecans |
url |
http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00004/full |
work_keys_str_mv |
AT despoinaebarbouri syndecansasmodulatorsandpotentialpharmacologicaltargetsincancerprogression AT nikolaoseafratis syndecansasmodulatorsandpotentialpharmacologicaltargetsincancerprogression AT chrisostomiegialeli syndecansasmodulatorsandpotentialpharmacologicaltargetsincancerprogression AT demitrioshvynios syndecansasmodulatorsandpotentialpharmacologicaltargetsincancerprogression AT achilleasdtheocharis syndecansasmodulatorsandpotentialpharmacologicaltargetsincancerprogression AT nikosekaramanos syndecansasmodulatorsandpotentialpharmacologicaltargetsincancerprogression |
_version_ |
1725466397785456640 |