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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Published inInternational journal of molecular sciences Vol. 21; no. 18; p. 6588
Main Authors De Pasquale, Valeria, Pavone, Luigi Michele
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 09.09.2020
MDPI
Subjects
Acids
Biosynthesis
Carcinogenesis
Collagen
Enzymes
Genes
Glycoproteins
Growth factors
Heparan sulfate
Heparan Sulfate Proteoglycans - chemistry
Heparan Sulfate Proteoglycans - metabolism
Humans
Ligands
Lung cancer
MAP Kinase Signaling System
Metastasis
Molecular Structure
Molecular Targeted Therapy
Mutation
Physiology
Prostate cancer
Proteins
Review
Signal transduction
Skin cancer
Thyroid cancer
Tumor Microenvironment
Tumors
remodeling
signaling
tumor microenvironment
heparan sulfate proteoglycans
extracellular matrix
Online AccessGet full text
ISSN1422-0067
1661-6596
1422-0067
DOI10.3390/ijms21186588

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Abstract 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.
AbstractList 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.
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.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.
Author Pavone, Luigi Michele
De Pasquale, Valeria
AuthorAffiliation 2 Department of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico II, 80131 Naples, Italy; luigimichele.pavone@unina.it
1 Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy
AuthorAffiliation_xml – name: 1 Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy
– name: 2 Department of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico II, 80131 Naples, Italy; luigimichele.pavone@unina.it
Author_xml – sequence: 1
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  orcidid: 0000-0001-5285-1980
  surname: De Pasquale
  fullname: De Pasquale, Valeria
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  givenname: Luigi Michele
  orcidid: 0000-0002-5145-7428
  surname: Pavone
  fullname: Pavone, Luigi Michele
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32916872$$D View this record in MEDLINE/PubMed
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Issue 18
Keywords remodeling
signaling
tumor microenvironment
heparan sulfate proteoglycans
extracellular matrix
Language English
License https://creativecommons.org/licenses/by/4.0
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Snippet In the last few decades, heparan sulfate (HS) proteoglycans (HSPGs) have been an intriguing subject of study for their complex structural characteristics,...
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StartPage 6588
SubjectTerms Acids
Biosynthesis
Carcinogenesis
Collagen
Enzymes
Genes
Glycoproteins
Growth factors
Heparan sulfate
Heparan Sulfate Proteoglycans - chemistry
Heparan Sulfate Proteoglycans - metabolism
Humans
Ligands
Lung cancer
MAP Kinase Signaling System
Metastasis
Molecular Structure
Molecular Targeted Therapy
Mutation
Physiology
Prostate cancer
Proteins
Review
Signal transduction
Skin cancer
Thyroid cancer
Tumor Microenvironment
Tumors
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Title Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment
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