File Download
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.3389/fcell.2021.673295
- Scopus: eid_2-s2.0-85107581102
- PMID: 34124056
- WOS: WOS:000660055700001
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: 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 |
---|---|
Authors | |
Keywords | tumor-associated M2 macrophages gastric cancer plexin domain containing 2 (PLXDC2) stroma EMT |
Issue Date | 2021 |
Publisher | Frontiers Research Foundation. The Journal's web site is located at https://www.frontiersin.org/journals/cell-and-developmental-biology |
Citation | Frontiers in Cell and Developmental Biology, 2021, v. 9, p. article no. 673295 How to Cite? |
Abstract | 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. |
Persistent Identifier | http://hdl.handle.net/10722/300707 |
ISSN | 2021 Impact Factor: 6.081 2020 SCImago Journal Rankings: 2.452 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Guan, Y | - |
dc.contributor.author | Du, Y | - |
dc.contributor.author | Wang, G | - |
dc.contributor.author | Gou, H | - |
dc.contributor.author | Xue, Y | - |
dc.contributor.author | Xu, J | - |
dc.contributor.author | Li, E | - |
dc.contributor.author | Chan, DW | - |
dc.contributor.author | Wu, D | - |
dc.contributor.author | Xu, P | - |
dc.contributor.author | Ni, P | - |
dc.contributor.author | Xu, D | - |
dc.contributor.author | Hu, Y | - |
dc.date.accessioned | 2021-06-18T14:55:54Z | - |
dc.date.available | 2021-06-18T14:55:54Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Frontiers in Cell and Developmental Biology, 2021, v. 9, p. article no. 673295 | - |
dc.identifier.issn | 2296-634X | - |
dc.identifier.uri | http://hdl.handle.net/10722/300707 | - |
dc.description.abstract | 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. | - |
dc.language | eng | - |
dc.publisher | Frontiers Research Foundation. The Journal's web site is located at https://www.frontiersin.org/journals/cell-and-developmental-biology | - |
dc.relation.ispartof | Frontiers in Cell and Developmental Biology | - |
dc.rights | This Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | tumor-associated M2 macrophages | - |
dc.subject | gastric cancer | - |
dc.subject | plexin domain containing 2 (PLXDC2) | - |
dc.subject | stroma | - |
dc.subject | EMT | - |
dc.title | Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer | - |
dc.type | Article | - |
dc.identifier.email | Chan, DW: dwchan@hku.hk | - |
dc.identifier.authority | Chan, DW=rp00543 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3389/fcell.2021.673295 | - |
dc.identifier.pmid | 34124056 | - |
dc.identifier.pmcid | PMC8194078 | - |
dc.identifier.scopus | eid_2-s2.0-85107581102 | - |
dc.identifier.hkuros | 322764 | - |
dc.identifier.volume | 9 | - |
dc.identifier.spage | article no. 673295 | - |
dc.identifier.epage | article no. 673295 | - |
dc.identifier.isi | WOS:000660055700001 | - |
dc.publisher.place | Switzerland | - |