ADH-1 suppresses N-cadherin-dependent pancreatic cancer progression

Yasushi Shintani, Yuri Fukumoto, Nina Chaika, Paul M. Grandgenett, Michael A. Hollingsworth, Margaret J. Wheelock, Keith R. Johnson

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Pancreatic cancer is one of the most aggressive malignant diseases. We recently reported that N-cadherin plays a key role in tumor progression and metastasis in pancreatic cancer. For this study, we sought to determine if an N-cadherin-blocking peptide (ADH-1) could prevent N-cadherin-mediated tumor progression in a mouse model for pancreatic cancer. The effect of ADH-1 on N-cadherin-mediated cell scattering and migration on collagen I was examined using pancreatic cancer cells. We also examined the influence of ADH-1 on cell apoptosis. Furthermore, in vivo animal studies were performed using orthotopic injection of N-cadherin overexpressing BxPC-3 cells with or without ADH-1 treatment. BxPC-3 and Capan-1 cells exhibited increased expression of N-cadherin in response to collagen I. This increase in N-cadherin promoted cell scattering and migration in response to collagen I. ADH-1 prevented these changes, but did not inhibit upregulation of N-cadherin. TUNEL assays and immunoblots for caspase-3 showed that ADH-1 induced apoptosis in a concentration dependent and N-cadherin dependent manner in pancreatic cancer cells. ADH-1 treatment resulted in significant reductions in tumor growth and lung metastasis in a mouse model for pancreatic cancer. The N-cadherin antagonist, ADH-1 has significant antitumor activity against N-cadherin-expressing cells using in vitro assays and in an orthotopic mouse model for pancreatic cancer, raising the possibility that N-cadherin antagonists have therapeutic potential for the treatment of pancreatic cancer in humans.

Original languageEnglish (US)
Pages (from-to)71-77
Number of pages7
JournalInternational Journal of Cancer
Volume122
Issue number1
DOIs
StatePublished - Jan 1 2008

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Keywords

  • ADH-1
  • N-cadherin
  • N-cadherin antagonist
  • Pancreatic cancer
  • Tumor invasion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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