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

Background-Phospholipase A(2) (PLA(2)) is involved in regulating biosynthesis of arachidonic acid and its metabolites. There are three major structurally different forms of PLA(2): group I, also called pancreatic PLA(2) (PLA(2)-I); group II, referred to as secretory non-pancreatic or synovial or platelet PLA(2) (PLA(2)-II); group IV, referred to as cytosolic PLA(2) (PLA(2)-IV). Aims-To examine PLA(2)-I, PLA(2)-II, and PLA(2)-IV in normal and pancreatic cancer tissues. Patients-PLA(2) 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 PLA(2) group 11 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 PLA(2)-I immunoreactivity was seen in acinar cells, but not in ductal cells, in the normal pancreas. In pancreatic cancer cells, PLA(2)-I immunostaining was absent. PLA(2)-II immunostaining was visible only in some acinar and ductal cells in the normal pancreas, whereas in pancreatic cancer increased PLA(2)-II immunoreactivity was present in 65% of the cancer samples. On in situ hybridisation, weak PLA(2)-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 PLA(2)-II in pancreatic cancer was associated with a higher degree of fibrosis (p < 0.01). Furthermore, there was a significant correlation between the enhanced expression of PLA(2)-II and longer survival after surgery (p < 0.03), but not of PLA(2)-IV and longer postoperative survival. Conclusion-These data suggest that PLA(2)-II and PLA(2)-IV are upregulated in human pancreatic cancer, and that upregulation of PLA(2)-II in pancreatic cancer covariates negatively with cancer cell covariates growth.