Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

Atsushi Kanno, Kennichi Satoh, Atsushi Masamune, Morihisa Hirota, Kenji Kimura, Jun Umino, Shin Hamada, Akihiko Satoh, Shinichi Egawa, Fuyuhiko Motoi, Michiaki Unno, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)

Abstract

Periostin is a secretory protein that has been suggested to function as a cell adhesion molecule and promote the invasiveness or growth rate of tumors. However, little is known about the association of its expression and epithelial to mesenchymal transition (EMT), which is considered to play a crucial role in cancer cell metastasis. Thus, the authors investigated whether periostin could be involved in the process of EMT and the role of this gene in pancreatic cancer development. The expression of periostin was observed mainly in stromal cells but very little in cancer cells by immunohistochemistry and real-time RT-PCR. In vitro, pancreatic stellate cells (PSCs) exhibited a much higher basal expression of periostin compared with cancer cells. Periostin secreted in the supernatant from 293T cells that expressed periostin (approximately 150 ng/ml) inhibited the migration of pancreatic cancer cells. Coculture assay revealed that periostin expression in PSC was induced by pancreatic cancer cells. To assess the direct role of periostin in pancreatic cancer cells, the authors generated pancreatic cancer cell lines that stably express periostin. The induced expression of periostin (to 150 ng/ml) altered the morphology of cancer cells, changing them from mesenchymal to epithelial phenotypes with the induction of epithelial markers and a reduction of mesenchymal markers, and showed reduced cell migration in vitro and formed smaller tumors as well as suppressed metastasis in vivo. On the other hand, high concentration of recombinant periostin (1 μg/ml) promoted cell migration with AKT activation. The findings suggest that periostin has biphasic effect on the development of pancreatic cancer.

Original languageEnglish
Pages (from-to)2707-2718
Number of pages12
JournalInternational Journal of Cancer
Volume122
Issue number12
DOIs
Publication statusPublished - 2008 Jun 15

Keywords

  • EMT
  • Pancreatic cancer
  • Pancreatic stellate cell
  • Periostin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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