Cargando…

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer

The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in...

Descripción completa

Detalles Bibliográficos
Autores principales: Guan, Yiming, Du, Yuzhang, Wang, Guanzheng, Gou, Hongquan, Xue, Yilun, Xu, Jingsong, Li, Enhao, Chan, David W., Wu, Di, Xu, Peiqing, Ni, Peihua, Xu, Dakang, Hu, Yiqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194078/
https://www.ncbi.nlm.nih.gov/pubmed/34124056
http://dx.doi.org/10.3389/fcell.2021.673295
_version_ 1783706348129615872
author Guan, Yiming
Du, Yuzhang
Wang, Guanzheng
Gou, Hongquan
Xue, Yilun
Xu, Jingsong
Li, Enhao
Chan, David W.
Wu, Di
Xu, Peiqing
Ni, Peihua
Xu, Dakang
Hu, Yiqun
author_facet Guan, Yiming
Du, Yuzhang
Wang, Guanzheng
Gou, Hongquan
Xue, Yilun
Xu, Jingsong
Li, Enhao
Chan, David W.
Wu, Di
Xu, Peiqing
Ni, Peihua
Xu, Dakang
Hu, Yiqun
author_sort Guan, Yiming
collection PubMed
description The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2’s correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process.
format Online
Article
Text
id pubmed-8194078
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81940782021-06-12 Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer Guan, Yiming Du, Yuzhang Wang, Guanzheng Gou, Hongquan Xue, Yilun Xu, Jingsong Li, Enhao Chan, David W. Wu, Di Xu, Peiqing Ni, Peihua Xu, Dakang Hu, Yiqun Front Cell Dev Biol Cell and Developmental Biology The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2’s correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process. Frontiers Media S.A. 2021-05-28 /pmc/articles/PMC8194078/ /pubmed/34124056 http://dx.doi.org/10.3389/fcell.2021.673295 Text en Copyright © 2021 Guan, Du, Wang, Gou, Xue, Xu, Li, Chan, Wu, Xu, Ni, Xu and Hu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Guan, Yiming
Du, Yuzhang
Wang, Guanzheng
Gou, Hongquan
Xue, Yilun
Xu, Jingsong
Li, Enhao
Chan, David W.
Wu, Di
Xu, Peiqing
Ni, Peihua
Xu, Dakang
Hu, Yiqun
Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer
title Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer
title_full Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer
title_fullStr Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer
title_full_unstemmed Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer
title_short Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer
title_sort overexpression of plxdc2 in stromal cell-associated m2 macrophages is related to emt and the progression of gastric cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194078/
https://www.ncbi.nlm.nih.gov/pubmed/34124056
http://dx.doi.org/10.3389/fcell.2021.673295
work_keys_str_mv AT guanyiming overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT duyuzhang overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT wangguanzheng overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT gouhongquan overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT xueyilun overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT xujingsong overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT lienhao overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT chandavidw overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT wudi overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT xupeiqing overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT nipeihua overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT xudakang overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer
AT huyiqun overexpressionofplxdc2instromalcellassociatedm2macrophagesisrelatedtoemtandtheprogressionofgastriccancer