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PMID: 1801923 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Lipoxygenase metabolites of arachidonic and linoleic acids modulate the adhesion of tumor cells to endothelium via regulation of protein kinase C.

Cell regulation ·Vol. 2 ·No. 12 ·1991-12-00 ·Pages 1045-55

Liu B, Timar J, Howlett J, Diglio CA, Honn KV

Abstract

12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE) and 13(S)-hydroxyoctadecadienoic acid (13[S]-HODE), lipoxygenase metabolites of arachidonic acid and linoleic acid, respectively, previously have been suggested to regulate tumor cell adhesion to endothelium during metastasis. Adhesion of rat Walker carcinosarcoma (W256) cells to a rat endothelial cell monolayer was enhanced after treatment with 12(S)-HETE and this 12(S)-HETE enhanced adhesion was blocked by 13(S)-HODE. Protein kinase inhibitors, staurosporine, calphostin C, and 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine, inhibited the 12(S)-HETE enhanced W256 cell adhesion. Depleting W256 cells of protein kinase C (PKC) with phorbol 12-myristate-13-acetate abolished their ability to respond to 12(S)-HETE. Treatment of W256 cells with 12(S)-HETE induced a 100% increase in membrane-associated PKC activity whereas 13(S)-HODE inhibited the effect of 12(S)-HETE on PKC translocation. High-performance liquid chromatographic analysis revealed that in W256 cells 12-HETE and 13-HODE were two of the major lipoxygenase metabilites of arachidonic acid and linoleic acid, respectively. Therefore, these two metabolites may provide an alternative signaling pathway for the regulation of PKC. Further, these findings suggest that the regulation of tumor cell adhesion to endothelium by 12(S)-HETE and 13(S)-HODE may be a PKC-dependent process.

MeSH Terms
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid Animals Arachidonic Acid/metabolism Cell Adhesion/drug effects Down-Regulation Endothelium, Vascular/cytology,drug effects Hydroxyeicosatetraenoic Acids/pharmacology Immunohistochemistry Linoleic Acid Linoleic Acids/metabolism,pharmacology Lipoxygenase/metabolism Protein Kinase C/antagonists & inhibitors,metabolism Tumor Cells, Cultured/drug effects,metabolism,pathology
Chemicals
Hydroxyeicosatetraenoic Acids Linoleic Acids Arachidonic Acid 13-hydroxy-9,11-octadecadienoic acid 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid Linoleic Acid Lipoxygenase Protein Kinase C
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Liu B
Department of Radiation Oncology, Wayne State University, Detroit, Michigan.
Timar J
Howlett J
Diglio C A
Honn K V
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35 references, click to expand
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Article Info
Journal
Cell regulation
Abbr.
Cell Regul
ISSN
1044-2030
Published
1991-12-00
Pages
1045-55
Language
English
Region
United States
NLM ID
9005331
PMCID
PMC361904
Subset
IM
Grants
NCI NIH HHS · CA 29997-07 · United States
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