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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...

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Autores principales: 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
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
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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.
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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
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