Prolidase activity disregulation in chronic pancreatitis and pancreatic cancer.
OBJECTIVE
One of the consequences of inflammatory diseases and neoplastic transformation is disregulation in metabolism of collagen and its interaction with cell surface integrin receptors. Although extracellular collagenases initiate the breakdown of tissue collagen the final step of collagen degradation is mediated by prolidase (E.C.3.4.13.9). We investigated whether prolidase activity may reflect disturbances of collagen metabolism in human pancreatitis and pancreatic cancer.


METHODS
Ten human samples of advanced chronic pancreatitis and pancreatic cancer and ten samples of normal pancreas were compared in respect to prolidase activity and expression (western immunoblot), collagen content (hydroxyproline determination), collagenolytic activity (zymography) and beta 1 integrin subunit expression (western immunoblot).


RESULTS
In pancreatitis tissue, an increase in collagen content, collagenolytic activity and beta 1 integrin expression were accompanied by significant decrease (about 2-fold) in prolidase activity and marked decrease in its expression, compared to normal pancreas. Pancreatic cancer tissue, compared to normal pancreas showed insignificant increase in collagen content, dramatic increase of collagenolytic activity and undetectable beta 1 integrin expression. These phenomena were accompanied by over 10-fold decrease in prolidase activity and marked decrease in prolidase expression.


CONCLUSIONS
The results suggest that prolidase activity may reflect the extent of disturbances in tissue collagen metabolism during pancreatic diseases and the level of its activity may serve as a marker of chronic pancreatitis and pancreatic cancer.
Palka
Jerzy
J
Department of Medicinal Chemistry, Medical Academy of Bialystok, ul. M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland.
Surazynski
Arkadiusz
A
Karna
Ewa
E
Orlowski
Kazimierz
K
Puchalski
Zbigniew
Z
Pruszynski
Krzysztof
K
Laszkiewicz
Joanna
J
Dzienis
Henryk
H
D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism*; D004150:Dipeptidases / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D010195:Pancreatitis / Q000201:enzymology*
D015415:Biomarkers; D016023:Integrins; D003094:Collagen; D004150:Dipeptidases; C022449:proline dipeptidase