論文

査読有り
2017年6月

Periostin suppresses in vivo invasiveness via PDK1/Akt/mTOR signaling pathway in a mouse orthotopic model of bladder cancer

ONCOLOGY LETTERS
  • Chul Jang Kim
  • ,
  • Yukihiro Tambe
  • ,
  • Ken-Ichi Mukaisho
  • ,
  • Hiroyuki Sugihara
  • ,
  • Susumu Kageyama
  • ,
  • Akihiro Kawauchi
  • ,
  • Hirokazu Inoue

13
6
開始ページ
4276
終了ページ
4284
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3892/ol.2017.6004
出版者・発行元
SPANDIDOS PUBL LTD

Periostin is an extracellular matrix protein involved in the regulation of intercellular adhesion. The present study investigated the in vivo tumor suppressor function of periostin in a mouse orthotopic model of bladder cancer. Retroviral vectors were used to transfect human bladder cancer UMUC-3 cell line with periostin. Bladders of nude mice that were transurethrally instilled with periostin-expressing UMUC-3 cells were revealed to weigh less compared with bladders instilled with vector control cells. In total, five (83.3%) of six vector control UMUC-3 bladder tumors exhibited histological evidence of muscle invasion. However, none of the five periostin-expressing UMUC-3 bladder tumors revealed muscle invasion. Thick edematous lesions were present in the submucosa of periostin-expressing UMUC-3 bladder tumors. The expression of periostin also suppressed in vitro cell invasiveness of UMUC-3 cells without affecting cellular proliferation. The level of phosphorylation of phosphoinositide-dependent kinase-1 (PDK1), protein kinase B (Akt) and S6 ribosomal protein, a downstream protein of mammalian target of rapamycin (mTOR) was decreased in periostin-expressing UMUC-3 cells compared with vector control cells. Treatment with 100 ng/ml recombinant human periostin protein also suppressed cell invasiveness and phosphorylation of PDK1, Akt and S6 in UMUC-3 cells, consistent with results using periostin-expressing UMUC-3 cells. Treatment with PDK1, Akt and mTOR inhibitors significantly suppressed UMUC-3 cell invasiveness. These results demonstrate that periostin suppresses in vivo and in vitro invasiveness of bladder cancer via the PDK1/Akt/mTOR signaling pathway. Periostin may be useful as a potent chemotherapeutic agent by suppressing bladder cancer invasiveness.

Web of Science ® 被引用回数 : 2

リンク情報
DOI
https://doi.org/10.3892/ol.2017.6004
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28599427
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000403909200040&DestApp=WOS_CPL