Ligand-independent activation of EphA2 by arachidonic acid induces metastasis-like behaviour in prostate cancer cells.
Details
Serval ID
serval:BIB_1E93527F8E1A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ligand-independent activation of EphA2 by arachidonic acid induces metastasis-like behaviour in prostate cancer cells.
Journal
British Journal of Cancer
ISSN
1532-1827 (Electronic)
ISSN-L
0007-0920
Publication state
Published
Issued date
2012
Volume
107
Number
10
Pages
1737-1744
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
BACKGROUND: High intake of omega-6 polyunsaturated fatty acids (PUFA) has been associated with clinical progression in prostate cancer (CaP). This study investigates the signalling mechanism by which the omega-6 PUFA arachidonic acid (AA) induces prostatic cellular migration to bone marrow stroma.
METHODS: Western blot analysis of the PC-3, PC3-GFP, DU 145 and LNCaP cells or their lipid raft (LR) components post AA stimulation was conducted in association with assays for adhesion and invasion through the bone marrow endothelial monolayers.
RESULTS: Arachidonic acid increased transendothelial migration of PC3-GFP cells (adhesion 37%±0.08, P=0.0124; transmigration 270%±0.145, P=0.0008). Akt, Src and focal adhesion kinase (FAK) pathways were induced by AA and integrally involved in transendothelial migration. LR were critical in AA uptake and induced Akt activity. Ephrin receptor A2 (EphA2), localised in LR, is expressed in DU 145 and PC-3 cells. Arachidonic acid induced a rapid increase of EphA2 Akt-dependent/ligand-independent activation, while knockdown of the EphrinA1 ligand decreased AA induced transendothelial migration, with an associated decrease in Src and FAK activity. Arachidonic acid activated Akt in EphA2(-) LNCaP cells but failed to induce BMEC transendothelial invasion.
CONCLUSION: Arachidonic acid induced stimulation of EphA2 in vitro is associated fundamentally with CaP epithelial migration across the endothelial barrier.
METHODS: Western blot analysis of the PC-3, PC3-GFP, DU 145 and LNCaP cells or their lipid raft (LR) components post AA stimulation was conducted in association with assays for adhesion and invasion through the bone marrow endothelial monolayers.
RESULTS: Arachidonic acid increased transendothelial migration of PC3-GFP cells (adhesion 37%±0.08, P=0.0124; transmigration 270%±0.145, P=0.0008). Akt, Src and focal adhesion kinase (FAK) pathways were induced by AA and integrally involved in transendothelial migration. LR were critical in AA uptake and induced Akt activity. Ephrin receptor A2 (EphA2), localised in LR, is expressed in DU 145 and PC-3 cells. Arachidonic acid induced a rapid increase of EphA2 Akt-dependent/ligand-independent activation, while knockdown of the EphrinA1 ligand decreased AA induced transendothelial migration, with an associated decrease in Src and FAK activity. Arachidonic acid activated Akt in EphA2(-) LNCaP cells but failed to induce BMEC transendothelial invasion.
CONCLUSION: Arachidonic acid induced stimulation of EphA2 in vitro is associated fundamentally with CaP epithelial migration across the endothelial barrier.
Keywords
Arachidonic Acid/pharmacology, Cell Line, Tumor, Cell Movement/drug effects, Cell Movement/genetics, Endothelium/metabolism, Endothelium/pathology, Ephrin-A1/genetics, Ephrin-A1/metabolism, Fatty Acids, Omega-6/pharmacology, Focal Adhesion Protein-Tyrosine Kinases/genetics, Focal Adhesion Protein-Tyrosine Kinases/metabolism, Genes, src, Humans, Ligands, Male, Mesenchymal Stromal Cells/metabolism, Mesenchymal Stromal Cells/pathology, Neoplasm Metastasis, Prostatic Neoplasms/genetics, Prostatic Neoplasms/metabolism, Proto-Oncogene Proteins c-akt/genetics, Proto-Oncogene Proteins c-akt/metabolism, Receptor, EphA2/genetics, Receptor, EphA2/metabolism, Signal Transduction/drug effects, Signal Transduction/genetics
Pubmed
Web of science
Open Access
Yes
Create date
10/09/2014 17:42
Last modification date
20/08/2019 13:54
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