TY - JOUR T1 - Group X Phospholipase A<sub>2</sub> Stimulates the Proliferation of Colon Cancer Cells by Producing Various Lipid Mediators JF - Molecular Pharmacology JO - Mol Pharmacol SP - 778 LP - 790 DO - 10.1124/mol.108.053371 VL - 76 IS - 4 AU - Fanny Surrel AU - Ikram Jemel AU - Eric Boilard AU - James G. Bollinger AU - Christine Payré AU - Carine M. Mounier AU - Kati A. Talvinen AU - Veli J. O. Laine AU - Timo J. Nevalainen AU - Michael H. Gelb AU - Gérard Lambeau Y1 - 2009/10/01 UR - http://molpharm.aspetjournals.org/content/76/4/778.abstract N2 - Among mammalian secreted phospholipases A2 (sPLA2s), the group X enzyme has the most potent hydrolyzing capacity toward phosphatidylcholine, the major phospholipid of cell membrane and lipoproteins. This enzyme has recently been implicated in chronic inflammatory diseases such as atherosclerosis and asthma and may also play a role in colon tumorigenesis. We show here that group X sPLA2 [mouse (m)GX] is one of the most highly expressed PLA2 in the mouse colon and that recombinant mouse and human enzymes stimulate proliferation and mitogen-activated protein kinase activation of various colon cell lines, including Colon-26 cancer cells. Among various recombinant sPLA2s, mGX is the most potent enzyme to stimulate cell proliferation. Based on the use of sPLA2 inhibitors, catalytic site mutants, and small interfering RNA silencing of cytosolic PLA2α and M-type sPLA2 receptor, we demonstrate that mGX promotes cell proliferation independently of the receptor and via its intrinsic catalytic activity and production of free arachidonic acid and lysophospholipids, which are mitogenic by themselves. mGX can also elicit the production of large amounts of prostaglandin E2 and other eicosanoids from Colon-26 cells, but these lipid mediators do not play a role in mGX-induced cell proliferation because inhibitors of cyclooxygenases and lipoxygenases do not prevent sPLA2 mitogenic effects. Together, our results indicate that group X sPLA2 may play an important role in colon tumorigenesis by promoting cancer cell proliferation and releasing various lipid mediators involved in other key events in cancer progression. © 2009 The American Society for Pharmacology and Experimental Therapeutics ER -