The lipoxygenase metabolite 12(S)-hete promotes α(IIb)β3 integrin-mediated tumor-cell spreading on fibronectin

J. Tímár, Y. Q. Chen, B. Liu, R. Bazaz, J. D. Taylor, K. V. Honn

Research output: Contribution to journalArticle

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Abstract

Tumor-cell interaction with the vessel wall during metastasis involves adhesion, induction of endothelial-cell retraction and spreading on the exposed sub-endothelial matrix. The signals for initiation of tumor-cell spreading and the receptors involved are unknown. A protocol was developed to distinguish between initial tumor-cell (B16 amelanotic melanoma; B16a) adhesion to and spreading on fibronectin. The time for maximum spreading was 50 min. Treatment with a lipoxygenase metabolite of arachidonic acid [12(S)-HETE] resulted in maximum spreading in 15 min (max. effect approx. 0.1 μM). Other lipoxygenase metabolites were ineffective. 12(S)-HETE treatment induced a rearrangement of F-actin, vinculin, vimentin intermediate filaments and integrin α(IIb)β3, but not integrin α5β1. Antibodies to (IIb)β3 but not α5β1 blocked the 12(S)-HETE effect on B16a spreading. B16a-cell attachment to fibronectin resulted in increased metabolism of arachidonic acid to 12(S)-HETE, which was inhibited by lipoxygenase but not by cyclo-oxygenase inhibitors. Accordingly, lipoxygenase inhibitors but not cyclooxygenase inhibitors blocked spontaneous B16a-cell spreading. The protein-kinase-C inhibitors calphostin C, H7 and staurosporine also inhibited spreading, while the protein-kinase-A inhibitor H8 was ineffective. These data suggest that B16a-cell spreading on fibronectin is initiated by a lipoxygenase metabolite [12(S)-HETE] of arachidonic acid and is mediated by protein kinase C.

Original languageEnglish
Pages (from-to)594-603
Number of pages10
JournalInternational Journal of Cancer
Volume52
Issue number4
DOIs
Publication statusPublished - 1992

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12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Arachidonate 12-Lipoxygenase
Fibronectins
Integrins
Lipoxygenase
Cyclooxygenase Inhibitors
Neoplasms
Protein Kinase Inhibitors
Arachidonic Acid
Protein Kinase C
Amelanotic Melanoma
Arachidonate Lipoxygenases
Vinculin
Lipoxygenase Inhibitors
Experimental Melanomas
Staurosporine
Intermediate Filaments
Protein C Inhibitor
Vimentin
Cyclic AMP-Dependent Protein Kinases

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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The lipoxygenase metabolite 12(S)-hete promotes α(IIb)β3 integrin-mediated tumor-cell spreading on fibronectin. / Tímár, J.; Chen, Y. Q.; Liu, B.; Bazaz, R.; Taylor, J. D.; Honn, K. V.

In: International Journal of Cancer, Vol. 52, No. 4, 1992, p. 594-603.

Research output: Contribution to journalArticle

Tímár, J. ; Chen, Y. Q. ; Liu, B. ; Bazaz, R. ; Taylor, J. D. ; Honn, K. V. / The lipoxygenase metabolite 12(S)-hete promotes α(IIb)β3 integrin-mediated tumor-cell spreading on fibronectin. In: International Journal of Cancer. 1992 ; Vol. 52, No. 4. pp. 594-603.
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