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

Kim,Chul  Jang; Tambe,Yukihiro; Mukaisho,Ken‑Ichi; Sugihara,Hiroyuki; Kageyama,Susumu; Kawauchi,Akihiro; Inoue,Hirokazu

doi:10.3892/ol.2017.6004

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

Authors:
- Chul Jang Kim
- Yukihiro Tambe
- Ken‑Ichi Mukaisho
- Hiroyuki Sugihara
- Susumu Kageyama
- Akihiro Kawauchi
- Hirokazu Inoue
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Affiliations: Department of Urology, Kohka Public Hospital, Kohka, Shiga 528‑6024, Japan, Division of Microbiology and Infectious Diseases, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan, Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan
Published online on: April 7, 2017 https://doi.org/10.3892/ol.2017.6004
Pages: 4276-4284
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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