Thrombin causes pseudopod detachment via a pathway involving cytosolic phospholipase A2 and 12/15-lipoxygenase products.
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.
Ross
S
S
Department of Cellular and Structural Biology and University of Colorado Cancer Center, University of Colorado School of Medicine, Denver 80262, USA.
Essary
B
B
de la Houssaye
B A
BA
Pan
Z
Z
Mikule
K
K
Mubarak
O
O
Pfenninger
K H
KH
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D001095:Arachidonic Acids / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000276:immunology; D015777:Eicosanoids / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D008297:Male; D008858:Microscopy, Phase-Contrast; D051419:Paxillin; D010446:Peptide Fragments / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010750:Phosphoproteins / Q000276:immunology; D011471:Prostatic Neoplasms; D011554:Pseudopodia / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D016608:Talin / Q000276:immunology; D013917:Thrombin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D003598:Cytoskeletal Proteins; D015777:Eicosanoids; D005227:Fatty Acids; D051419:Paxillin; D010446:Peptide Fragments; D010750:Phosphoproteins; C496063:Pxn protein, rat; C118678:SFLLRNPND; D016608:Talin; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin