期刊
BRITISH JOURNAL OF CANCER
卷 107, 期 10, 页码 1737-1744出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2012.457
关键词
Ephrin A2; omega-6; bone marrow endothelial cells; bone marrow stroma; prostate cancer; metastasis
类别
资金
- Swiss National Science Foundation: 'Bourse chercheur debutant' [PBLAP3-129433/1]
- Swiss National Science Foundation: 'Bourse pour chercheur avance aupres FSBMB/Novartis' [PASMP3_134378/1]
- GU Cancer Research Group
- Christie Hospital based 'Men Matter' Charity
- Swiss National Science Foundation (SNF) [PBLAP3-129433] Funding Source: Swiss National Science Foundation (SNF)
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. British Journal of Cancer (2012) 107, 1737-1744. doi:10.1038/bjc.2012.457 www.bjcancer.com Published online 4 October 2012 (C) 2012 Cancer Research UK
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