Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression
Heparan sulfate (HS) are complex unbranched carbohydrate chains that are heavily modified by sulfate and exist either conjugated to proteins or as free, unconjugated chains. Proteins with covalently bound Heparan sulfate chains are termed Heparan Sulfate Proteoglycans (HSPGs). Both HS and HSPGs bind...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-08-01
|
Series: | Frontiers in Endocrinology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2018.00483/full |
id |
doaj-4632c4086a3244a890e10eff7690ec2c |
---|---|
record_format |
Article |
spelling |
doaj-4632c4086a3244a890e10eff7690ec2c2020-11-24T21:41:43ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-08-01910.3389/fendo.2018.00483344366Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and ProgressionArvindhan Nagarajan0Parmanand Malvi1Narendra Wajapeyee2Narendra Wajapeyee3Department of Pathology, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Pathology, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Pathology, Yale University School of Medicine, New Haven, CT, United StatesYale Cancer Center, Yale University School of Medicine, New Haven, CT, United StatesHeparan sulfate (HS) are complex unbranched carbohydrate chains that are heavily modified by sulfate and exist either conjugated to proteins or as free, unconjugated chains. Proteins with covalently bound Heparan sulfate chains are termed Heparan Sulfate Proteoglycans (HSPGs). Both HS and HSPGs bind to various growth factors and act as co-receptors for different cell surface receptors. They also modulate the dynamics and kinetics of various ligand-receptor interactions, which in turn can influence the duration and potency of the signaling. HS and HSPGs have also been shown to exert a structural role as a component of the extracellular matrix, thereby altering processes such as cell adhesion, immune cell infiltration and angiogenesis. Previous studies have shown that HS are deregulated in a variety of solid tumors and hematological malignancies and regulate key aspects of cancer initiation and progression. HS deregulation in cancer can occur as a result of changes in the level of HSPGs or due to changes in the levels of HS biosynthesis and remodeling enzymes. Here, we describe the major cell-autonomous (proliferation, apoptosis/senescence and differentiation) and cell-non-autonomous (angiogenesis, immune evasion, and matrix remodeling) roles of HS and HSPGs in cancer. Finally, we discuss therapeutic opportunities for targeting deregulated HS biosynthesis and HSPGs as a strategy for cancer treatment.https://www.frontiersin.org/article/10.3389/fendo.2018.00483/fullheparan sulfateheparan sulfate proteoglycanscancerimmune evasionsignaling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Arvindhan Nagarajan Parmanand Malvi Narendra Wajapeyee Narendra Wajapeyee |
spellingShingle |
Arvindhan Nagarajan Parmanand Malvi Narendra Wajapeyee Narendra Wajapeyee Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression Frontiers in Endocrinology heparan sulfate heparan sulfate proteoglycans cancer immune evasion signaling |
author_facet |
Arvindhan Nagarajan Parmanand Malvi Narendra Wajapeyee Narendra Wajapeyee |
author_sort |
Arvindhan Nagarajan |
title |
Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression |
title_short |
Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression |
title_full |
Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression |
title_fullStr |
Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression |
title_full_unstemmed |
Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression |
title_sort |
heparan sulfate and heparan sulfate proteoglycans in cancer initiation and progression |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2018-08-01 |
description |
Heparan sulfate (HS) are complex unbranched carbohydrate chains that are heavily modified by sulfate and exist either conjugated to proteins or as free, unconjugated chains. Proteins with covalently bound Heparan sulfate chains are termed Heparan Sulfate Proteoglycans (HSPGs). Both HS and HSPGs bind to various growth factors and act as co-receptors for different cell surface receptors. They also modulate the dynamics and kinetics of various ligand-receptor interactions, which in turn can influence the duration and potency of the signaling. HS and HSPGs have also been shown to exert a structural role as a component of the extracellular matrix, thereby altering processes such as cell adhesion, immune cell infiltration and angiogenesis. Previous studies have shown that HS are deregulated in a variety of solid tumors and hematological malignancies and regulate key aspects of cancer initiation and progression. HS deregulation in cancer can occur as a result of changes in the level of HSPGs or due to changes in the levels of HS biosynthesis and remodeling enzymes. Here, we describe the major cell-autonomous (proliferation, apoptosis/senescence and differentiation) and cell-non-autonomous (angiogenesis, immune evasion, and matrix remodeling) roles of HS and HSPGs in cancer. Finally, we discuss therapeutic opportunities for targeting deregulated HS biosynthesis and HSPGs as a strategy for cancer treatment. |
topic |
heparan sulfate heparan sulfate proteoglycans cancer immune evasion signaling |
url |
https://www.frontiersin.org/article/10.3389/fendo.2018.00483/full |
work_keys_str_mv |
AT arvindhannagarajan heparansulfateandheparansulfateproteoglycansincancerinitiationandprogression AT parmanandmalvi heparansulfateandheparansulfateproteoglycansincancerinitiationandprogression AT narendrawajapeyee heparansulfateandheparansulfateproteoglycansincancerinitiationandprogression AT narendrawajapeyee heparansulfateandheparansulfateproteoglycansincancerinitiationandprogression |
_version_ |
1725920365807403008 |