Kaufmann Simone, Kuphal Silke, Schubert Thomas, Bosserhoff Anja K
Institute of Pathology, University Hospital, University of Regensburg, Regensburg, Germany.
Cell Oncol. 2009;31(6):415-22. doi: 10.3233/CLO-2009-0491.
Malignant melanoma cells are known to have altered expression of genes supporting proliferation and invasion, however, the expression of molecules of the Netrin family of repellent factors has not been analyzed in melanomas until now.
Here, we show that Netrin-1 expression is strongly induced in melanoma cells compared to melanocytes in vivo and in vitro controlled at the transcriptional level via ETS-1. In addition, the expression of the netrin receptor UNC5B was induced and that of UNC5C was reduced in the tumor cells. In order to determine the functional relevance of Netrin-1 expression in malignant melanoma, Netrin expression in melanoma cells was reduced by siRNA attempts and primary human melanocytes were treated with recombinant Netrin-1. The cells showed no changes in proliferation or apoptosis, however, a strong reduction of migratory properties was observed in the melanoma cells after reduction of Netrin expression whereas melanocyte migration was strongly induced by treatment with Netrin.
Our study suggests that Netrin-1 promotes melanoma cell invasion and migration and therefore has an important role in the progression of malignant melanoma.
已知恶性黑色素瘤细胞中支持增殖和侵袭的基因表达发生改变，然而，迄今为止尚未对黑色素瘤中排斥因子Netrin家族分子的表达进行分析。
在此，我们表明，与体内和体外的黑素细胞相比，黑色素瘤细胞中Netrin-1的表达通过ETS-1在转录水平上受到强烈诱导。此外，肿瘤细胞中Netrin受体UNC5B的表达被诱导，而UNC5C的表达降低。为了确定Netrin-1表达在恶性黑色素瘤中的功能相关性，通过小干扰RNA（siRNA）尝试降低黑色素瘤细胞中的Netrin表达，并使用重组Netrin-1处理原代人黑素细胞。细胞在增殖或凋亡方面没有变化，然而，在Netrin表达降低后，黑色素瘤细胞的迁移特性显著降低，而用Netrin处理则强烈诱导黑素细胞迁移。
我们的研究表明，Netrin-1促进黑色素瘤细胞的侵袭和迁移，因此在恶性黑色素瘤的进展中起重要作用。
