Activities of phospholipase A2 and diacylglycerol lipase are increased in human colorectal cancer

Abstract

Experimental, clinical and epidemiological studies have implicated arachidonic acid and its metabolites as important mediators in colorectal carcinogenesis. Although arachidonic acid levels are increased in tumour membrane lipids, its availability for metabolic processes is not known. The activities of phospholipase A₂ (PLA₂) and diacylglycerol lipase therefore were assessed in tumour and normal mucosal specimens from 20 patients with colorectal cancer using ¹⁴C‐radiolabelled substrates. The median (interquartile range) PLA₂ activity was increased in tumour tissue (10.5 (6.0, 18.5) pmol arachidonic acid mg⁻¹ h⁻¹) compared with that in normal mucosa (5.6 (2.5, 8.5) pmol arachidonic acid mg⁻¹ h⁻¹) (P < 0.001, Wilcoxon signed rank test). Activity of diacylglycerol lipase was also greater in tumoral tissue (47.4 (21.6, 82.1) pmol arachidonic acid mg⁻¹ h⁻¹) than in mucosa (19.1 (9.4, 42.9) pmol arachidonic acid mg⁻¹ h⁻¹) (P < 0.005). There was no correlation between either PLA₂ or diacylglycerol lipase activity and myeloperoxidase activity, suggesting that these increases were not directly attributable to tumour inflammatory cell infiltrate. Augmentation of arachidonic acid release in colorectal tumours may have implications for therapy.