Anandamide inhibits adhesion and migration of breast cancer cells

Claudia Grimaldi, Simona Pisanti, Chiara Laezza, Anna Maria Malfitano, Antonietta Santoro, Mario Vitale, Maria Gabriella Caruso, Maria Notarnicola, Irma Iacuzzo, Giuseppe Portella, Vincenzo Di Marzo, Maurizio Bifulco

Research output: Contribution to journalArticle

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 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 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.

Original languageEnglish
Pages (from-to)363-373
Number of pages11
JournalExperimental Cell Research
Volume312
Issue number4
DOIs
Publication statusPublished - Feb 15 2006

Keywords

  • Cancer
  • Endocannabinoid
  • Metastasis

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    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), 363-373. https://doi.org/10.1016/j.yexcr.2005.10.024