Joseph Jan, Niggemann Bernd, Zaenker Kurt S, Entschladen Frank
Institute of Immunology, Witten/Herdecke University, Stockumer Str. 10, 58448, Witten, Germany.
Cancer Immunol Immunother. 2004 Aug;53(8):723-8. doi: 10.1007/s00262-004-0509-9. Epub 2004 Mar 18.
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.
细胞迁移在诸如免疫监视等生理过程中至关重要，在肿瘤细胞迁移和转移发展的病理过程中也同样重要。因此，调节这种肿瘤细胞迁移的因素，尤其是神经递质，一直是深入研究的焦点。虽然大多数神经递质对细胞迁移有刺激作用，但我们在此报告内源性物质花生四烯乙醇胺对肿瘤细胞和淋巴细胞迁移均有抑制作用。使用基于胶原蛋白的三维迁移试验和延时视频显微镜，我们观察到花生四烯乙醇胺介导的CD8 + T淋巴细胞和SW 480结肠癌细胞信号分别由不同的大麻素受体（CB-Rs）介导。使用特异性激动剂二十二碳四烯酰乙醇胺（DEA），我们观察到去甲肾上腺素诱导的结肠癌细胞迁移受到CB1-R的抑制。然而，如使用特异性激动剂JWH 133所示，SDF-1诱导的CD8 + T淋巴细胞迁移通过CB2-R受到抑制。因此，通过CB1-R参与特异性抑制肿瘤细胞迁移可能是一种选择性工具，可防止转移形成，而不会对癌症患者的免疫系统产生不利影响。
