論文

査読有り 国際誌
2019年6月21日

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

Oncology research
  • 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
  • 全て表示

27
6
開始ページ
713
終了ページ
727
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3727/096504018X15433161908259

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.

リンク情報
DOI
https://doi.org/10.3727/096504018X15433161908259
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30850029
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848439
ID情報
  • DOI : 10.3727/096504018X15433161908259
  • ISSN : 0965-0407
  • PubMed ID : 30850029
  • PubMed Central 記事ID : PMC7848439

エクスポート
BibTeX RIS