Preferential expression of cystein-rich secretory protein-3 (CRISP-3) in chronic pancreatitis.
Chronic pancreatitis (CP) is a progressive inflammatory process resulting in exocrine and endocrine pancreatic insufficiency in advanced stages. Cysteine-rich secretory protein (CRISP-3) has been identified as a defense-associated molecule with predominant expression in the salivary gland, pancreas and prostate.



In this study, we investigated CRISP-3 expression in normal pancreatic tissues, chronic pancreatitis tissues, pancreatic cancer tissues and pancreatic cancer cell lines, as well as in other gastrointestinal organs.



15 normal pancreatic tissues, 14 chronic pancreatitis tissues and 14 pancreatic cancer tissues as well as three pancreatic cancer cell lines were analyzed. Moreover, hepatocellular carcinoma and esophageal, stomach and colon cancers were also analyzed together with the corresponding normal controls.



CRISP-3 was expressed at moderate to high levels in chronic pancreatitis tissues and at moderate levels in pancreatic cancer tissues but at low levels in normal pancreatic tissues, and was absent in three pancreatic cancer cell lines. CRISP-3 expression was below the level of detection in all cancerous gastrointestinal tissues and in all normal tissues except 2 of 16 colon tissue samples. CRISP-3 mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells and in small proliferating ductal cells in CP tissues and CP-like lesions in pancreatic cancer tissues. In contrast, CRISP-3 expression was weak to absent in the cytoplasm of cancer cells as well as in acinar cells and ductal cells in pancreatic cancer tissues and normal pancreatic tissues.



These results reveal that the distribution of CRISP-3 in gastrointestinal tissues is predominantly in the pancreas. High levels of CRISP-3 in acinar cells dedifferentiating into small proliferating ductal cells in CP and CP-like lesions in pancreatic cancer suggests a role of this molecule in the pathophysiology of CP.
Liao
Q
Q
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Kleeff
J
J
Xiao
Y
Y
Guweidhi
A
A
Schambony
A
A
Töpfer-Petersen
E
E
Zimmermann
A
A
Büchler
M W
MW
Friess
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D015153:Blotting, Western; D002908:Chronic Disease; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010195:Pancreatitis / Q000378:metabolism*; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D012471:Salivary Proteins and Peptides / Q000096:biosynthesis*; D029589:Seminal Plasma Proteins / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
C489926:CRISP3 protein, human; D015347:RNA Probes; D012333:RNA, Messenger; D012471:Salivary Proteins and Peptides; D029589:Seminal Plasma Proteins