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

Introduction: ZO-1 is a tight junction membrane protein that plays a critic al role in cell-cell interaction, proliferation, and differentiation. Aim: To localize and evaluate the expression of ZO-1 in the normal human pa ncreas, in pancreatic ductal adenocarcinoma (PDAC), and in chronic pancreat itis (CP). Methodology and Results: Northern and Western blot analysis revealed ZO-1 e xpression in all six tested pancreatic cancer cell lines. Expression of ZO- 1 mRNA was increased sixfold in PDAC samples in comparison with normal samp les (p = 0.04). Confocal microscopy revealed the presence of ZO-1 in the ap ical and apicolateral areas of ductular cells in the normal pancreas. Simil arly, in CP, ZO-1 was localized at apical and apicolateral areas of small p roliferating ductular cells and large metaplastic ducts. In PDAC, however, ZO-1 expression was observed irrespective of whether the cancer cells forme d duct-like structures or exhibited a diffuse infiltrating pattern. Metasta tic pancreatic cancer cells within lymph nodes displayed variable staining patterns, ranging from apical and apicolateral to a diffuse membranous stai ning. Conclusion: These observations suggest that ZO-1 is overexpressed in PDAC a nd raise the possibility that this overexpression may confer a metastatic a dvantage to pancreatic cancer cells.