Anandamide is an endogenous inhibitor for the migration of tumor cells and T lymphocytes
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Cell migration is of paramount importance in physiological processes such as immune surveillance, but also in the pathological processes of tumor cell migration and metastasis development. The factors that regulate this tumor cell migration, most prominently neurotransmitters, have thus been the focus of intense investigation. While the majority of neurotransmitters have a stimulatory effect on cell migration, we herein report the inhibitory effect of the endogenous substance anandamide on both tumor cell and lymphocyte migration. Using a collagen-based three-dimensional migration assay and time-lapse videomicroscopy, we have observed that the anandamide-mediated signals for CD8+ T lymphocytes and SW 480 colon carcinoma cells are each mediated by distinct cannabinoid receptors (CB-Rs). Using the specific agonist docosatetraenoylethanolamide (DEA), we have observed that the norepinephrine-induced migration of colon carcinoma cells is inhibited by the CB1-R. The SDF-1–induced migration of CD8+ T lymphocytes was, however, inhibited via the CB2-R, as shown by using the specific agonist JWH 133. Therefore, specific inhibition of tumor cell migration via CB1-R engagement might be a selective tool to prevent metastasis formation without depreciatory effects on the immune system of cancer patients.
KeywordsAnandamide Cannabinoid receptors Cell migration T lymphocytes Tumor cells
This study was supported by the Fritz Bender Foundation, Munich, Germany, and the Bruno and Helene Joester Foundation, Cologne, Germany. We thank Beate Mainusch for excellent technical assistance and Theodore L. Drell IV for critical reading of the manuscript.
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