Thrombin causes pseudopod detachment via a pathway involving cytosolic phospholipase A2 and 12/15-lipoxygenase products

Abstract

Thrombin causes rapid pseudopod detachment and shortening in Dunning rat prostatic carcinoma (MAT-Lu) cells. As seen by interference reflection microscopy and by immunofluorescence analysis with antibodies to paxillin and talin, the primary event is disassembly of adhesion sites. Biochemically, thrombin is a potent activator of cytosolic phospholipase A2 and increases eicosanoid production in these cells. The pseudopod effects are blocked by lipoxygenase (but not cyclooxygenase) inhibitors. Arachidonic acid and 12(S)-hydroxyeicosatetraenoic acid or 15(S)-hydroxyeicosatetraenoic acid mimic the thrombin effect. We conclude that in certain cancer cells, thrombin is a pseudopod repellent that exerts its effect via a cascade involving cytosolic phospholipase A2, 12/15-lipoxygenase, and 12(S)- and/or 15(S)-hydroxyeicosatetraenoic acid.