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Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression

As a pancreatic inflammatory marker, regenerating islet-derived protein 3A (Reg3A) plays a key role in inflammation-associated pancreatic carcinogenesis by promoting cell proliferation, inhibiting apoptosis, and regulating cancer cell migration and invasion. This study aimed to reveal a novel immuno...

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Autores principales: Guo, Jie, Liao, Mengfan, Hu, Xianmin, Wang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490200/
https://www.ncbi.nlm.nih.gov/pubmed/34504050
http://dx.doi.org/10.14348/molcells.2021.0145
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author Guo, Jie
Liao, Mengfan
Hu, Xianmin
Wang, Jun
author_facet Guo, Jie
Liao, Mengfan
Hu, Xianmin
Wang, Jun
author_sort Guo, Jie
collection PubMed
description As a pancreatic inflammatory marker, regenerating islet-derived protein 3A (Reg3A) plays a key role in inflammation-associated pancreatic carcinogenesis by promoting cell proliferation, inhibiting apoptosis, and regulating cancer cell migration and invasion. This study aimed to reveal a novel immuno-regulatory mechanism by which Reg3A modulates tumour-promoting responses during pancreatic cancer (PC) progression. In an in vitro Transwell system that allowed the direct co-culture of human peripheral blood-derived dendritic cells (DCs) and Reg3A-overexpressing/ silenced human PC cells, PC cell-derived Reg3A was found to downregulate CD80, CD83 and CD86 expression on educated DCs, increase DC endocytic function, inhibit DC-induced T lymphocyte proliferation, reduce IL-12p70 production, and enhance IL-23 production by DCs. The positive effect of tumour-derived Reg3A-educated human DCs on PC progression was demonstrated in vivo by intraperitoneally transferring them into PC-implanted severe combined immunodeficiency (SCID) mice reconstituted with human T cells. A Reg3A-JAK2/STAT3 positive feedback loop was identified in DCs educated with Reg3A. In conclusion, as a tumour-derived factor, Reg3A acted to block the differentiation and maturation of the most important antigen-presenting cells, DCs, causing them to limit their potential anti-tumour responses, thus facilitating PC escape and progression.
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spelling pubmed-84902002021-10-08 Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression Guo, Jie Liao, Mengfan Hu, Xianmin Wang, Jun Mol Cells Research Article As a pancreatic inflammatory marker, regenerating islet-derived protein 3A (Reg3A) plays a key role in inflammation-associated pancreatic carcinogenesis by promoting cell proliferation, inhibiting apoptosis, and regulating cancer cell migration and invasion. This study aimed to reveal a novel immuno-regulatory mechanism by which Reg3A modulates tumour-promoting responses during pancreatic cancer (PC) progression. In an in vitro Transwell system that allowed the direct co-culture of human peripheral blood-derived dendritic cells (DCs) and Reg3A-overexpressing/ silenced human PC cells, PC cell-derived Reg3A was found to downregulate CD80, CD83 and CD86 expression on educated DCs, increase DC endocytic function, inhibit DC-induced T lymphocyte proliferation, reduce IL-12p70 production, and enhance IL-23 production by DCs. The positive effect of tumour-derived Reg3A-educated human DCs on PC progression was demonstrated in vivo by intraperitoneally transferring them into PC-implanted severe combined immunodeficiency (SCID) mice reconstituted with human T cells. A Reg3A-JAK2/STAT3 positive feedback loop was identified in DCs educated with Reg3A. In conclusion, as a tumour-derived factor, Reg3A acted to block the differentiation and maturation of the most important antigen-presenting cells, DCs, causing them to limit their potential anti-tumour responses, thus facilitating PC escape and progression. Korean Society for Molecular and Cellular Biology 2021-09-30 2021-09-10 /pmc/articles/PMC8490200/ /pubmed/34504050 http://dx.doi.org/10.14348/molcells.2021.0145 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ (https://creativecommons.org/licenses/by-nc-sa/3.0/)
spellingShingle Research Article
Guo, Jie
Liao, Mengfan
Hu, Xianmin
Wang, Jun
Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression
title Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression
title_full Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression
title_fullStr Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression
title_full_unstemmed Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression
title_short Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression
title_sort tumour-derived reg3a educates dendritic cells to promote pancreatic cancer progression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490200/
https://www.ncbi.nlm.nih.gov/pubmed/34504050
http://dx.doi.org/10.14348/molcells.2021.0145
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