Anandamide inhibits adhesion and migration of breast cancer cells

Journal Article · Wed Feb 15 04:00:00 EST 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.10.024· OSTI ID:20775337

Grimaldi, Claudia ^[1]; Pisanti, Simona ^[1]; Laezza, Chiara ^[2]; Malfitano, Anna Maria ^[1]; Santoro, Antonietta ^[1]; Vitale, Mario ^[3]; Caruso, Maria Gabriella ^[4]; Notarnicola, Maria ^[4]; Iacuzzo, Irma ^[1]; Portella, Giuseppe ^[2]; Di Marzo, Vincenzo ^[5]; Bifulco, Maurizio ^[6]

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1. Dipartimento di Scienze Farmaceutiche, Endocannabinoid Research Group, Universita degli Studi di Salerno, Fisciano (Italy)
2. Istituto di Endocrinologia e Oncologia Sperimentale del CNR e Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita di Napoli Federico II (Italy)
3. Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Universita di Napoli Federico II (Italy)
4. Laboratorio di Biochimica, IRCCS 'S. de Bellis', Castellana Grotte (Bari) (Italy)
5. Istituto di Chimica Biomolecolare, C.N.R., Pozzuoli (Namibia) (Italy)
6. Dipartimento di Scienze Farmaceutiche, Endocannabinoid Research Group, Universita degli Studi di Salerno, Fisciano (Sa) (Italy)

The endocannabinoid system regulates cell proliferation in human breast cancer cells. We reasoned that stimulation of cannabinoid CB{sub 1} receptors could induce a non-invasive phenotype in breast mtastatic 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 CB{sub 1} 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 CB{sub 1} receptor agonists inhibit tumor cell invasion and metastasis by modulating FAK phosphorylation, and that CB{sub 1} receptor activation might represent a novel therapeutic strategy to slow down the growth of breast carcinoma and to inhibit its metastatic diffusion in vivo.

• OSTI ID: 20775337
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 4 Vol. 312; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOMAS
CELL PROLIFERATION
COLLAGEN
IN VITRO
IN VIVO
MAMMARY GLANDS
METASTASES
PHENOTYPE
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RECEPTORS
TUMOR CELLS
TYROSINE