Cargando…
Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers
The fertile stroma in pancreatic ductal adenocarcinomas (PDACs) has been suspected to greatly contribute to PDAC progression. Since the main cell constituents of the stroma are fibroblasts, there is crosstalking(s) between PDAC cells and surrounding fibroblasts in the stroma, which induces a fibrobl...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cognizant Communication Corporation
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848439/ https://www.ncbi.nlm.nih.gov/pubmed/30850029 http://dx.doi.org/10.3727/096504018X15433161908259 |
_version_ | 1783645137071505408 |
---|---|
author | Takamatsu, Hitoshi Yamamoto, Ken-ichi Tomonobu, Nahoko Murata, Hitoshi Inoue, Yusuke Yamauchi, Akira Sumardika, I Wayan Chen, Youyi Kinoshita, Rie Yamamura, Masahiro Fujiwara, Hideyo Mitsui, Yosuke Araki, Kota Futami, Junichiro Saito, Ken Iioka, Hidekazu Ruma, I Made Winarsa Putranto, Endy Widya Nishibori, Masahiro Kondo, Eisaku Yamamoto, Yasuhiko Toyooka, Shinichi Sakaguchi, Masakiyo |
author_facet | Takamatsu, Hitoshi Yamamoto, Ken-ichi Tomonobu, Nahoko Murata, Hitoshi Inoue, Yusuke Yamauchi, Akira Sumardika, I Wayan Chen, Youyi Kinoshita, Rie Yamamura, Masahiro Fujiwara, Hideyo Mitsui, Yosuke Araki, Kota Futami, Junichiro Saito, Ken Iioka, Hidekazu Ruma, I Made Winarsa Putranto, Endy Widya Nishibori, Masahiro Kondo, Eisaku Yamamoto, Yasuhiko Toyooka, Shinichi Sakaguchi, Masakiyo |
author_sort | Takamatsu, Hitoshi |
collection | PubMed |
description | The fertile stroma in pancreatic ductal adenocarcinomas (PDACs) has been suspected to greatly contribute to PDAC progression. Since the main cell constituents of the stroma are fibroblasts, there is crosstalking(s) between PDAC cells and surrounding fibroblasts in the stroma, which induces a fibroblast proliferation burst. We have reported that several malignant cancer cells including PDAC cells secrete a pronounced level of S100A11, which in turn stimulates proliferation of cancer cells via the receptor for advanced glycation end products (RAGE) in an autocrine manner. Owing to the RAGE(+) expression in fibroblasts, the extracellular abundant S100A11 will affect adjacent fibroblasts. In this study, we investigated the significance of the paracrine axis of S100A11–RAGE in fibroblasts for their proliferation activity. In in vitro settings, extracellular S100A11 induced upregulation of fibroblast proliferation. Our mechanistic studies revealed that the induction is through RAGE–MyD88–mTOR–p70 S6 kinase upon S100A11 stimulation. The paracrine effect on fibroblasts is linked mainly to triggering growth but not cellular motility. Thus, the identified pathway might become a potential therapeutic target to suppress PDAC progression through preventing PDAC-associated fibroblast proliferation. |
format | Online Article Text |
id | pubmed-7848439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cognizant Communication Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78484392021-02-16 Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers Takamatsu, Hitoshi Yamamoto, Ken-ichi Tomonobu, Nahoko Murata, Hitoshi Inoue, Yusuke Yamauchi, Akira Sumardika, I Wayan Chen, Youyi Kinoshita, Rie Yamamura, Masahiro Fujiwara, Hideyo Mitsui, Yosuke Araki, Kota Futami, Junichiro Saito, Ken Iioka, Hidekazu Ruma, I Made Winarsa Putranto, Endy Widya Nishibori, Masahiro Kondo, Eisaku Yamamoto, Yasuhiko Toyooka, Shinichi Sakaguchi, Masakiyo Oncol Res Article The fertile stroma in pancreatic ductal adenocarcinomas (PDACs) has been suspected to greatly contribute to PDAC progression. Since the main cell constituents of the stroma are fibroblasts, there is crosstalking(s) between PDAC cells and surrounding fibroblasts in the stroma, which induces a fibroblast proliferation burst. We have reported that several malignant cancer cells including PDAC cells secrete a pronounced level of S100A11, which in turn stimulates proliferation of cancer cells via the receptor for advanced glycation end products (RAGE) in an autocrine manner. Owing to the RAGE(+) expression in fibroblasts, the extracellular abundant S100A11 will affect adjacent fibroblasts. In this study, we investigated the significance of the paracrine axis of S100A11–RAGE in fibroblasts for their proliferation activity. In in vitro settings, extracellular S100A11 induced upregulation of fibroblast proliferation. Our mechanistic studies revealed that the induction is through RAGE–MyD88–mTOR–p70 S6 kinase upon S100A11 stimulation. The paracrine effect on fibroblasts is linked mainly to triggering growth but not cellular motility. Thus, the identified pathway might become a potential therapeutic target to suppress PDAC progression through preventing PDAC-associated fibroblast proliferation. Cognizant Communication Corporation 2019-06-21 /pmc/articles/PMC7848439/ /pubmed/30850029 http://dx.doi.org/10.3727/096504018X15433161908259 Text en Copyright © 2019 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License. |
spellingShingle | Article Takamatsu, Hitoshi Yamamoto, Ken-ichi Tomonobu, Nahoko Murata, Hitoshi Inoue, Yusuke Yamauchi, Akira Sumardika, I Wayan Chen, Youyi Kinoshita, Rie Yamamura, Masahiro Fujiwara, Hideyo Mitsui, Yosuke Araki, Kota Futami, Junichiro Saito, Ken Iioka, Hidekazu Ruma, I Made Winarsa Putranto, Endy Widya Nishibori, Masahiro Kondo, Eisaku Yamamoto, Yasuhiko Toyooka, Shinichi Sakaguchi, Masakiyo Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers |
title | Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers |
title_full | Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers |
title_fullStr | Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers |
title_full_unstemmed | Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers |
title_short | Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers |
title_sort | extracellular s100a11 plays a critical role in spread of the fibroblast population in pancreatic cancers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848439/ https://www.ncbi.nlm.nih.gov/pubmed/30850029 http://dx.doi.org/10.3727/096504018X15433161908259 |
work_keys_str_mv | AT takamatsuhitoshi extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT yamamotokenichi extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT tomonobunahoko extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT muratahitoshi extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT inoueyusuke extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT yamauchiakira extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT sumardikaiwayan extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT chenyouyi extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT kinoshitarie extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT yamamuramasahiro extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT fujiwarahideyo extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT mitsuiyosuke extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT arakikota extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT futamijunichiro extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT saitoken extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT iiokahidekazu extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT rumaimadewinarsa extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT putrantoendywidya extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT nishiborimasahiro extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT kondoeisaku extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT yamamotoyasuhiko extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT toyookashinichi extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers AT sakaguchimasakiyo extracellulars100a11playsacriticalroleinspreadofthefibroblastpopulationinpancreaticcancers |