RRC ID 60114
著者 Takamatsu H, Yamamoto KI, Tomonobu N, Murata H, Inoue Y, Yamauchi A, Sumardika IW, Chen Y, Kinoshita R, Yamamura M, Fujiwara H, Mitsui Y, Araki K, Futami J, Saito K, Iioka H, Ruma IMW, Putranto EW, Nishibori M, Kondo E, Yamamoto Y, Toyooka S, Sakaguchi M.
タイトル Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers.
ジャーナル Oncol Res
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.
巻・号 27(6)
ページ 713-727
公開日 2019-6-21
DOI 10.3727/096504018X15433161908259
PMID 30850029
PMC PMC7848439
MeSH Animals Cancer-Associated Fibroblasts / metabolism Cancer-Associated Fibroblasts / pathology Carcinoma, Pancreatic Ductal / metabolism Carcinoma, Pancreatic Ductal / pathology Cell Line Cell Line, Tumor Cell Movement Cell Proliferation Extracellular Space / metabolism Fibroblasts / metabolism* Fibroblasts / pathology Humans Immunohistochemistry Mice Models, Biological Myeloid Differentiation Factor 88 / metabolism Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology* Receptor for Advanced Glycation End Products / metabolism Ribosomal Protein S6 Kinases, 70-kDa / metabolism S100 Proteins / metabolism* TOR Serine-Threonine Kinases / metabolism Tumor Microenvironment
IF 4.634
引用数 1
リソース情報
ヒト・動物細胞 PK-8(RCB2700)