The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells
The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells
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DOI：
10.1007/s10549-007-9504-0
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发表时间：
2007-12-01
影响因子：
3.8
通讯作者：
Zeillinger, Robert
中科院分区：
文献类型：
--
作者：
Schmid, Bernd C.;Rezniczek, Guenther A.;Zeillinger, Robert
细胞迁移在许多不同的过程中都是必不可少的，从胚胎发育到伤口愈合和免疫反应。最近发现癌细胞利用趋化因子及其受体介导的趋化机制，例如通常在白细胞中发现的CXCL12/CXCR4通路。在这里，我们展示了Slit2，一种分泌的蛋白质，通过环绕式(Robo)受体作为轴突引导和神经元迁移的化学排斥剂发出信号，对乳腺癌细胞起着强大的化学吸引作用。比较特定转移到脑或骨的细胞系，我们发现它们对CXCL12和Slit2治疗的反应有显著差异，表明Sit/Robo信号在脑转移中发挥作用。
Cell migration is essential in many diverse processes ranging from embryonic development to wound healing and immune response. Cancer cells have recently been shown to utilize chemoattraction mechanisms mediated by chemokines and their respective receptors, e.g., the CXCL12/CXCR4 pathway normally found in leukocytes. Here we show that Slit2, a secreted protein signaling through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, acts as a potent chemoattractant for breast cancer cells. Comparing cell lines specifically metastasizing to either brain or bone, we found significant differences in their responses to CXCL12 and Slit2 treatments, suggesting a role for Slit/Robo signaling in brain metastasis.