Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

In the last few decades, heparan sulfate (HS) proteoglycans (HSPGs) have been an intriguing subject of study for their complex structural characteristics, their finely regulated biosynthetic machinery, and the wide range of functions they perform in living organisms from development to adulthood. Fr...

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Main Authors: Valeria De Pasquale, Luigi Michele Pavone
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/18/6588
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author Valeria De Pasquale
Luigi Michele Pavone
author_facet Valeria De Pasquale
Luigi Michele Pavone
author_sort Valeria De Pasquale
collection DOAJ
description In the last few decades, heparan sulfate (HS) proteoglycans (HSPGs) have been an intriguing subject of study for their complex structural characteristics, their finely regulated biosynthetic machinery, and the wide range of functions they perform in living organisms from development to adulthood. From these studies, key roles of HSPGs in tumor initiation and progression have emerged, so that they are currently being explored as potential biomarkers and therapeutic targets for cancers. The multifaceted nature of HSPG structure/activity translates in their capacity to act either as inhibitors or promoters of tumor growth and invasion depending on the tumor type. Deregulation of HSPGs resulting in malignancy may be due to either their abnormal expression levels or changes in their structure and functions as a result of the altered activity of their biosynthetic or remodeling enzymes. Indeed, in the tumor microenvironment, HSPGs undergo structural alterations, through the shedding of proteoglycan ectodomain from the cell surface or the fragmentation and/or desulfation of HS chains, affecting HSPG function with significant impact on the molecular interactions between cancer cells and their microenvironment, and tumor cell behavior. Here, we overview the structural and functional features of HSPGs and their signaling in the tumor environment which contributes to tumorigenesis and cancer progression.
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spelling doaj.art-509af2294c1d44459bf979215afae2832023-11-20T13:04:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118658810.3390/ijms21186588Heparan Sulfate Proteoglycan Signaling in Tumor MicroenvironmentValeria De Pasquale0Luigi Michele Pavone1Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico II, 80131 Naples, ItalyIn the last few decades, heparan sulfate (HS) proteoglycans (HSPGs) have been an intriguing subject of study for their complex structural characteristics, their finely regulated biosynthetic machinery, and the wide range of functions they perform in living organisms from development to adulthood. From these studies, key roles of HSPGs in tumor initiation and progression have emerged, so that they are currently being explored as potential biomarkers and therapeutic targets for cancers. The multifaceted nature of HSPG structure/activity translates in their capacity to act either as inhibitors or promoters of tumor growth and invasion depending on the tumor type. Deregulation of HSPGs resulting in malignancy may be due to either their abnormal expression levels or changes in their structure and functions as a result of the altered activity of their biosynthetic or remodeling enzymes. Indeed, in the tumor microenvironment, HSPGs undergo structural alterations, through the shedding of proteoglycan ectodomain from the cell surface or the fragmentation and/or desulfation of HS chains, affecting HSPG function with significant impact on the molecular interactions between cancer cells and their microenvironment, and tumor cell behavior. Here, we overview the structural and functional features of HSPGs and their signaling in the tumor environment which contributes to tumorigenesis and cancer progression.https://www.mdpi.com/1422-0067/21/18/6588tumor microenvironmentextracellular matrixheparan sulfate proteoglycansremodelingsignaling
spellingShingle Valeria De Pasquale
Luigi Michele Pavone
Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment
International Journal of Molecular Sciences
tumor microenvironment
extracellular matrix
heparan sulfate proteoglycans
remodeling
signaling
title Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment
title_full Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment
title_fullStr Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment
title_full_unstemmed Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment
title_short Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment
title_sort heparan sulfate proteoglycan signaling in tumor microenvironment
topic tumor microenvironment
extracellular matrix
heparan sulfate proteoglycans
remodeling
signaling
url https://www.mdpi.com/1422-0067/21/18/6588
work_keys_str_mv AT valeriadepasquale heparansulfateproteoglycansignalingintumormicroenvironment
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