Growth of human pancreatic cancer cells, induced by human pancreatic phospholipase A(2), is mediated via its specific receptor but not via its catalytic property

Abstract

Human pancreatic phospholipase A(2) type I (hPLA(2)-I) has been found to stimulate the growth of human pancreatic cancer cell line, MIAPaCa-2, which has a receptor for PLA(2). In the present study, half-maximal inhibitory concentrations (IC(50)s) for the mature- and pro-form of hPLA(2)-I and certain eukaryotic and prokaryotic PLA(2)s were determined using ligand binding studies. The IC50 for the mature form was 3.5x10(-9) M compared to those for the pro-form and non-human PLA(2)s (over 5.0x10(-7) M), suggesting receptor specificity for mature hPLA(2)-I. Receptor binding was independent of Ca2+, which is required for PLA(2)'s digestive activity. Lysophospholipids, generated by PLA(2), showed no proliferative effect on the MIAPaCa-2 cells. Furthermore, MIAPaCa-2 cells treated with hPLA(2)-I did not release fatty acids. This implies that proliferation of these cells is mediated by binding of hPLA(2)-I to the specific receptor, not by its enzymatic activity. The hPLA(2)-I induced cell proliferation was blocked by preincubation of the enzyme with anti-hPLA(2)-I monoclonal antibody.