Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers

Overview

Journal Oncol Res

Specialty Oncology

Date 2019 Mar 10

PMID 30850029

Citations 16

Authors

Hitoshi Takamatsu

Ken-Ichi Yamamoto

Nahoko Tomonobu

Hitoshi Murata

Yusuke Inoue

Akira Yamauchi

I Wayan Sumardika

Youyi Chen

Rie Kinoshita

Masahiro Yamamura

Hideyo Fujiwara

Yosuke Mitsui

Kota Araki

Junichiro Futami

Ken Saito

Hidekazu Iioka

I Made Winarsa Ruma

Endy Widya Putranto

Masahiro Nishibori

Eisaku Kondo

Yasuhiko Yamamoto

Shinichi Toyooka

Masakiyo Sakaguchi

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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