A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells

Summary: Myeloid-derived suppressor cells (MDSCs) infiltrate cancer tissue, promote tumor growth, and are associated with resistance to cancer therapies. However, there is no practical approach available to distinguish MDSCs from mature counterparts inside tumors. Here, we show that a recently isola...

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Autores principales: Thomas Welte, Junhua Mai, Zhe Zhang, Shaohui Tian, Guodong Zhang, Yitian Xu, Licheng Zhang, Shu-shia Chen, Tian Wang, Haifa Shen
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Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/7c73f5260e8348c5902ad6ec129b4de4
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spelling oai:doaj.org-article:7c73f5260e8348c5902ad6ec129b4de42021-11-20T05:10:21ZA heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells2589-004210.1016/j.isci.2021.103349https://doaj.org/article/7c73f5260e8348c5902ad6ec129b4de42021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013183https://doaj.org/toc/2589-0042Summary: Myeloid-derived suppressor cells (MDSCs) infiltrate cancer tissue, promote tumor growth, and are associated with resistance to cancer therapies. However, there is no practical approach available to distinguish MDSCs from mature counterparts inside tumors. Here, we show that a recently isolated thioaptamer probe (T1) binds to MDSC subsets in colorectal and pancreatic tumors with high specificity. Whole transcriptome and functional analysis revealed that T1-binding cells contain polymorphonuclear (PMN)-MDSCs characterized by several immunosuppression pathways, ROS production, and T cell suppression activity, whereas T1-non-binding PMNs were mature and nonsuppressive. We identified syndecan-1 as the T1-interacting protein on MDSCs and chronic myelogenous leukemia K562 cell line. Heparan sulfate chains were essential in T1-binding. Inside tumors PMN-MDSCs expressed heparan sulfate biogenesis enzymes at higher levels. Tumor-cell-derived soluble factor(s) enhanced MDSCs' affinity for T1. Overall, we uncovered heparan-sulfate-dependent MDSC modulation in the tumor microenvironment and identified T1 as tool preferentially targeting tumor-promoting myeloid cell subsets.Thomas WelteJunhua MaiZhe ZhangShaohui TianGuodong ZhangYitian XuLicheng ZhangShu-shia ChenTian WangHaifa ShenElsevierarticleMolecular biologyImmunologyCell biologyScienceQENiScience, Vol 24, Iss 11, Pp 103349- (2021)
institution DOAJ
collection DOAJ
language EN
topic Molecular biology
Immunology
Cell biology
Science
Q
spellingShingle Molecular biology
Immunology
Cell biology
Science
Q
Thomas Welte
Junhua Mai
Zhe Zhang
Shaohui Tian
Guodong Zhang
Yitian Xu
Licheng Zhang
Shu-shia Chen
Tian Wang
Haifa Shen
A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells
description Summary: Myeloid-derived suppressor cells (MDSCs) infiltrate cancer tissue, promote tumor growth, and are associated with resistance to cancer therapies. However, there is no practical approach available to distinguish MDSCs from mature counterparts inside tumors. Here, we show that a recently isolated thioaptamer probe (T1) binds to MDSC subsets in colorectal and pancreatic tumors with high specificity. Whole transcriptome and functional analysis revealed that T1-binding cells contain polymorphonuclear (PMN)-MDSCs characterized by several immunosuppression pathways, ROS production, and T cell suppression activity, whereas T1-non-binding PMNs were mature and nonsuppressive. We identified syndecan-1 as the T1-interacting protein on MDSCs and chronic myelogenous leukemia K562 cell line. Heparan sulfate chains were essential in T1-binding. Inside tumors PMN-MDSCs expressed heparan sulfate biogenesis enzymes at higher levels. Tumor-cell-derived soluble factor(s) enhanced MDSCs' affinity for T1. Overall, we uncovered heparan-sulfate-dependent MDSC modulation in the tumor microenvironment and identified T1 as tool preferentially targeting tumor-promoting myeloid cell subsets.
format article
author Thomas Welte
Junhua Mai
Zhe Zhang
Shaohui Tian
Guodong Zhang
Yitian Xu
Licheng Zhang
Shu-shia Chen
Tian Wang
Haifa Shen
author_facet Thomas Welte
Junhua Mai
Zhe Zhang
Shaohui Tian
Guodong Zhang
Yitian Xu
Licheng Zhang
Shu-shia Chen
Tian Wang
Haifa Shen
author_sort Thomas Welte
title A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells
title_short A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells
title_full A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells
title_fullStr A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells
title_full_unstemmed A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells
title_sort heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells
publisher Elsevier
publishDate 2021
url https://doaj.org/article/7c73f5260e8348c5902ad6ec129b4de4
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