Anandamide inhibits adhesion and migration of breast cancer cells

被引:146
作者
Grimaldi, C
Pisanti, S
Laezza, C
Malfitano, AM
Santoro, A
Vitale, M
Caruso, MG
Notarnicola, M
Iacuzzo, I
Portella, G
Di Marzo, V [1 ]
Bifulco, M
机构
[1] Univ Salerno, Dipartimento Sci Farmaceut, Endocannabinoid Res Grp, Fisciano, Sa, Italy
[2] CNR, Ist Endocrinol & Oncol Sperimentale, I-00185 Rome, Italy
[3] Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, Naples, Italy
[4] Univ Naples Federico II, Dipartimento Endocrinol & Oncol Mol & Clin, Naples, Italy
[5] IRCCS S de Bellis, Biochim Lab, Bari, Italy
[6] CNR, Ist Chim Biomol, Pozzuoli, NA, Italy
关键词
endocannabinoid; cancer; metastasis;
D O I
10.1016/j.yexcr.2005.10.024
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The endocannabinoid system regulates cell proliferation in human breast cancer cells. We reasoned that stimulation of cannabinoid CB1 receptors could induce a non-invasive phenotype in breast metastatic cells. In a model of metastatic spreading in vivo, the metabolically stable anandamide analogue, 2-methyl-2'-F-anandamide (Met-F-AEA), significantly reduced the number and dimension of metastatic nodes, this effect being antagonized by the selective CB1 antagonist SR141716A. In MDA-MB-231 cells, a highly invasive human breast cancer cell line, and in TSA-E1 cells, a murine breast cancer cell line, Met-F-AEA inhibited adhesion and migration on type IV collagen in vitro without modifying integrin expression: both these effects were antagonized by SR141716A. In order to understand the molecular mechanism involved in these processes, we analyzed the phosphorylation of FAK and Src, two tyrosine kinases involved in migration and adhesion. In Met-F-AEA-treated cells, we observed a decreased tyrosine phosphorylation of both FAK and Src, this effect being attenuated by SR141716A. We propose that CB1 receptor agonists inhibit tumor cell invasion and metastasis by modulating FAK phosphorylation, and that CB1 receptor activation might represent a novel therapeutic strategy to slow down the growth of breast carcinoma and to inhibit its metastatic diffusion in vivo. (C) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:363 / 373
页数:11
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