Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer

J. Kleeff, X. Shi, H. P. Bode, K. Hoover, S. Shrikhande, P. J. Bryant, M. Korc, M. W. Büchler, H. Friess

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Introduction: ZO-1 is a tight junction membrane protein that plays a critical role in cell-cell interaction, proliferation, and differentiation. Aim: To localize and evaluate the expression of ZO-1 in the normal human pancreas, in pancreatic ductal adenocarcinoma (PDAC), and in chronic pancreatitis (CP). Methodology and Results: Northern and Western blot analysis revealed ZO-1 expression in all six tested pancreatic cancer cell lines. Expression of ZO-1 mRNA was increased sixfold in PDAC samples in comparison with normal samples (p = 0.04). Confocal microscopy revealed the presence of ZO-1 in the apical and apicolateral areas of ductular cells in the normal pancreas. Similarly, in CP, ZO-1 was localized at apical and apicolateral areas of small proliferating ductular cells and large metaplastic ducts. In PDAC, however, ZO-1 expression was observed irrespective of whether the cancer cells formed ductlike structures or exhibited a diffuse infiltrating pattern. Metastatic pancreatic cancer cells within lymph nodes displayed variable staining patterns, ranging from apical and apicolateral to a diffuse membranous staining. Conclusion: These observations suggest that ZO-1 is overexpressed in PDAC and raise the possibility that this overexpression may confer a metastatic advantage to pancreatic cancer cells.

Original languageEnglish (US)
Pages (from-to)259-265
Number of pages7
JournalPancreas
Volume23
Issue number3
DOIs
StatePublished - Oct 10 2001

Keywords

  • Chronic pancreatitis
  • MAGUK
  • Pancreatic cancer
  • Pancreatic ductal adenocarcinoma
  • Tight junction
  • Tumor suppressor

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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    Kleeff, J., Shi, X., Bode, H. P., Hoover, K., Shrikhande, S., Bryant, P. J., Korc, M., Büchler, M. W., & Friess, H. (2001). Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer. Pancreas, 23(3), 259-265. https://doi.org/10.1097/00006676-200110000-00006