Group II and IV phospholipase A2 are produced in human pancreatic cancer cells and influence prognosis

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Abstract
BACKGROUND Phospholipase A2 (PLA2) is involved in regulating biosynthesis of arachidonic acid and its metabolites. There are three major structurally different forms of PLA2: group I, also called pancreatic PLA2 (PLA2-I); group II, referred to as secretory non-pancreatic or synovial or platelet PLA2 (PLA2-II); group IV, referred to as cytosolic PLA2 (PLA2-IV). AIMS To examine PLA2-I, PLA2-II, and PLA2-IV in normal and pancreatic cancer tissues. Patients—PLA2 was studied in 58 pancreatic adenocarcinomas, obtained from 25 women and 33 men undergoing pancreatic resection. Normal organ donor pancreas served as control. METHODS The enzymes were analysed by northern blot, in situ hybridisation, and immunohistochemistry. The molecular findings were correlated with clinical variables of the patients. RESULTS Northern blot analysis of total RNA showed enhanced PLA2 group II and IV mRNA expression in 52% and 55% of the pancreatic cancer samples respectively compared with the normal controls (p = 0.0013 and p = 0.0025). On immunohistochemical analysis, intense PLA2-I immunoreactivity was seen in acinar cells, but not in ductal cells, in the normal pancreas. In pancreatic cancer cells, PLA2-I immunostaining was absent. PLA2-II immunostaining was visible only in some acinar and ductal cells in the normal pancreas, whereas in pancreatic cancer increased PLA2-II immunoreactivity was present in 65% of the cancer samples. On in situ hybridisation, weak PLA2-IV mRNA signals were detected in acinar and ductal cells of normal samples; these signals were present to a much greater extent in pancreatic cancer cells. The presence of PLA2-II in pancreatic cancer was associated with a higher degree of fibrosis (p2-II and longer survival after surgery (p2-IV and longer postoperative survival. CONCLUSION These data suggest that PLA2-II and PLA2-IV are upregulated in human pancreatic cancer, and that upregulation of PLA2-II in pancreatic cancer covariates negatively with cancer cell growth.

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