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Anandamide inhibits adhesion and migration of breast cancer cells.
Exp Cell Res. 2006 Feb 15; 312(4):363-73.EC

Abstract

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.

Authors+Show Affiliations

Dipartimento di Scienze Farmaceutiche, Endocannabinoid Research Group, Università degli Studi di Salerno, Fisciano (Sa), Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16343481

Citation

Grimaldi, Claudia, et al. "Anandamide Inhibits Adhesion and Migration of Breast Cancer Cells." Experimental Cell Research, vol. 312, no. 4, 2006, pp. 363-73.
Grimaldi C, Pisanti S, Laezza C, et al. Anandamide inhibits adhesion and migration of breast cancer cells. Exp Cell Res. 2006;312(4):363-73.
Grimaldi, C., Pisanti, S., Laezza, C., Malfitano, A. M., Santoro, A., Vitale, M., Caruso, M. G., Notarnicola, M., Iacuzzo, I., Portella, G., Di Marzo, V., & Bifulco, M. (2006). Anandamide inhibits adhesion and migration of breast cancer cells. Experimental Cell Research, 312(4), 363-73.
Grimaldi C, et al. Anandamide Inhibits Adhesion and Migration of Breast Cancer Cells. Exp Cell Res. 2006 Feb 15;312(4):363-73. PubMed PMID: 16343481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anandamide inhibits adhesion and migration of breast cancer cells. AU - Grimaldi,Claudia, AU - Pisanti,Simona, AU - Laezza,Chiara, AU - Malfitano,Anna Maria, AU - Santoro,Antonietta, AU - Vitale,Mario, AU - Caruso,Maria Gabriella, AU - Notarnicola,Maria, AU - Iacuzzo,Irma, AU - Portella,Giuseppe, AU - Di Marzo,Vincenzo, AU - Bifulco,Maurizio, Y1 - 2005/12/15/ PY - 2005/05/06/received PY - 2005/10/24/revised PY - 2005/10/28/accepted PY - 2005/12/14/pubmed PY - 2006/3/3/medline PY - 2005/12/14/entrez SP - 363 EP - 73 JF - Experimental cell research JO - Exp Cell Res VL - 312 IS - 4 N2 - 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. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/16343481/Anandamide_inhibits_adhesion_and_migration_of_breast_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(05)00509-4 DB - PRIME DP - Unbound Medicine ER -