Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer.
BACKGROUND
ZO-1 is a tight junction membrane protein that plays a critical role in cell-cell interaction, proliferation, and differ entiation.


OBJECTIVE
To localize and evaluate the expression of ZO-1 in the normal human pancreas, in pancreatic ductal adenocarcinoma (PDAC), and in chronic pancreatitis (CP).


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 duct-like 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.


CONCLUSIONS
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.
Kleeff
J
J
Department of Visceral and Transplantation Surgery, University of Bern, Switzerland.
Shi
X
X
Bode
H P
HP
Hoover
K
K
Shrikhande
S
S
Bryant
P J
PJ
Korc
M
M
Büchler
M W
MW
Friess
H
H
D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry* / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics*; D018613:Microscopy, Confocal; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010179:Pancreas / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein