Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

Yoko Matsuda, Zenya Naito, Kiyoko Kawahara, Nando Nakazawa, Murray Korc, Toshiyuki Ishiwata

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Nestin, is a class VI intermediate filament (IF) that is expressed in 30% of pancreatic ductal adenocarcinoma (PDAC) cases, and its expression in PDAC positively correlates with peripancreatic invasion. An expression vector carrying a short hairpin RNA (shRNA) targeting nestin was stably transfected into PA NC-1 and PK-45H human pancreatic cancer cells, which express high nestin levels. Alterations in morphology and alignment of actin filaments and α-tubulin were examined by phase-contrast and immunocytochemistry. Effects on cell growth, migration in scratch and Boyden chamber assays, invasion, cell adhesion, and in vivo growth were determined. Differences in mRNA levels were examined by arrays. Nestin shRNA-transfected cells exhibited decreased nestin expression, a sheet-like appearance with tight cell-cell adhesion, increased expression of filamentous F-actin and E-cadherin, and attenuated migration and invasion, both of which were enhanced following nestin re-expression. Expression of α-tubulin, and in vitro cell growth and adhesion were not altered by nestin downregulation, whereas hepatic metastases were decreased. Thus, nestin plays important roles in pancreatic cancer cell migration, invasion and metastasis by selectively modulating the expression of actin and cell adhesion molecules, and may therefore be a novel therapeutic target in PDAC.

Original languageEnglish (US)
Pages (from-to)512-523
Number of pages12
JournalCancer Biology and Therapy
Volume11
Issue number5
DOIs
StatePublished - Mar 1 2011

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Keywords

  • Actin
  • Cell-cell adhesion
  • E-cadherin
  • Invasion
  • Migration
  • Nestin
  • Pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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