Institute of Pathology, University of Regensburg, Regensburg, Germany.
Int J Mol Med. 2011 Nov;28(5):721-6. doi: 10.3892/ijmm.2011.742. Epub 2011 Jul 8.
The repellent factor family of Slit molecules has been described to have repulsive function in the developing nervous system on growing axons expressing the Robo receptors. Alterations of the Slit/Robo system have been observed in various pathological conditions and in cancer. However, until today no detailed studies on Slit function on melanoma migration are available. Therefore, we analysed the mRNA expression in melanoma cells and found induction of Robo3 expression compared to normal melanocytes. Functional assays performed with melanoma cells revealed that treatment with Slit3 led to strong inhibition of migration. Interestingly, we observed down-regulation of AP-1 activity and target gene expression after Slit3 treatment contributing to the negative regulation of migration. Taken together, our data showed that Slit3 reduces the migratory activity of melanoma cells, potentially by repulsion of the cells in analogy to the neuronal system. Further studies will be necessary to prove Slit activity in vivo, but due to its function, Slit3 activity may be helpful in the treatment of melanoma.
Slit 分子的排斥因子家族已被描述为在表达 Robo 受体的生长轴突的发育神经系统中具有排斥功能。在各种病理条件和癌症中都观察到 Slit/Robo 系统的改变。然而，直到今天，关于 Slit 对黑色素瘤迁移的功能还没有详细的研究。因此，我们分析了黑色素瘤细胞中的 mRNA 表达，发现与正常黑素细胞相比，Robo3 的表达被诱导。用黑色素瘤细胞进行的功能分析表明，Slit3 的处理导致迁移的强烈抑制。有趣的是，我们观察到 Slit3 处理后 AP-1 活性和靶基因表达下调，这有助于迁移的负调控。总之，我们的数据表明 Slit3 降低了黑色素瘤细胞的迁移活性，可能类似于神经元系统的细胞排斥。还需要进一步的研究来证明 Slit 在体内的活性，但由于其功能，Slit3 的活性可能有助于黑色素瘤的治疗。
