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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Arachidonate 12-Lipoxygenase / metabolism*
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Arachidonate 15-Lipoxygenase / metabolism*
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Arachidonic Acids / pharmacology
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Cell Adhesion / drug effects
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Cell Movement
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Cytoskeletal Proteins / immunology
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Eicosanoids / pharmacology
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Fatty Acids / pharmacology
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Fluorescent Antibody Technique
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Male
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Microscopy, Phase-Contrast
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Paxillin
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Peptide Fragments / pharmacology
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Phospholipases A / metabolism*
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Phospholipases A2
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Phosphoproteins / immunology
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Prostatic Neoplasms
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Pseudopodia / drug effects*
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Rats
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Rats, Inbred Strains
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Talin / immunology
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Thrombin / pharmacology*
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Tumor Cells, Cultured
Substances
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Arachidonic Acids
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Cytoskeletal Proteins
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Eicosanoids
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Fatty Acids
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Paxillin
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Peptide Fragments
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Phosphoproteins
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Pxn protein, rat
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SFLLRNPND
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Talin
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Arachidonate 12-Lipoxygenase
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Arachidonate 15-Lipoxygenase
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Phospholipases A
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Phospholipases A2
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Thrombin