Hepatocyte growth factor/scatter factor facilitates migration of GN-11 immortalized LHRH neurons
Hepatocyte growth factor/scatter factor facilitates migration of GN-11 immortalized LHRH neurons
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DOI：
10.1210/en.2002-220146
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发表时间：
2002-09-01
期刊：
影响因子：
4.8
通讯作者：
Fasolo, A
中科院分区：
文献类型：
--
作者：
Giacobini, P;Giampietro, C;Fasolo, A
调节 LHRH 神经元从嗅觉基板迁移到大脑的过程的分子线索尚不清楚，但目标分泌的趋化因子和趋化因子的梯度可能在引导机制中发挥关键作用。肝细胞生长因子/分散因子 (HGF/SF) 是一种诱导细胞迁移的多效性细胞因子。它通过与其受体 c-Met 相互作用参与多种发育过程。在这里，我们展示了 c-Met 抗体标记了 E12 小鼠嗅觉间质中 LHRH 迁移神经元，并分析了 HGF/SF 对分别从下丘脑和嗅球中发育的肿瘤分离的两种永生化 LHRH 细胞系 GT1-7 和 GN11 的潜在趋化作用。 通过免疫细胞化学，我们提供了 GN11 细胞中 c-Met 高水平表达的证据，但 GT1-7 细胞中却没有。此外，胶原蛋白凝胶测定、延时视频显微镜和博伊登室实验证明，HGF/SF 治疗可促进 GN11 细胞的特异性迁移活性。这种促进作用被中和抗体抑制。这里报告的数据代表了 HGF/SF 对永生化 LHRH 神经元的趋化作用的第一个直接证据。
The molecular cues regulating the migratory process of LHRH neurons from the olfactory placode into the brain are not well known, but gradients of chemotropic and chemorepellent factors secreted by the targets are likely to play a key role in guidance mechanisms.Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic cytokine inducing cell migration. It is involved in a variety of developmental processes through interaction with its receptor c-Met. Here we show that c-Met-antibody labels LHRH migrating neurons in the olfactory mesenchyme of E12 mouse and analyze the potential chemotropic effect of HGF/SF on two immortalized LHRH cell lines, GT1-7 and GN11, isolated from tumors developed in the hypothalamus and in the olfactory bulb, respectively.By RT-PCR analysis, Western blotting, and immunocytochemistry, we provide evidence for a high level of c-Met expression in GN11, but not in GT1-7, cells. In addition, HGF/SF treatment promotes specific migratory activity of GN11 cells, as demonstrated by collagen gel assay, time-lapse video microscopy, and Boyden's chamber experiments. Such promotion is inhibited by the neutralizing antibody.The data reported here represent the first direct evidence of a chemotactic effect of HGF/SF on immortalized LHRH neurons.