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PTPμ suppresses glioma cell migration and dispersal

机译：PTPμ抑制神经胶质瘤细胞的迁移和扩散

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摘要

The cell-surface receptor protein tyrosine phosphatase mu (PTPμ) is a homophilic cell adhesion molecule expressed in CNS neurons and glia. Glioblastomas (GBMs) are the highest grade of primary brain tumors with astrocytic similarity and are characterized by marked dispersal of tumor cells. PTPμ expression was examined in human GBM, low-grade astrocytoma, and normal brain tissue. These studies revealed a striking loss of PTPμ protein expression in highly dispersive GBMs compared to less dispersive low-grade astrocytomas and normal brain. We hypothesized that PTPμ contributes to contact inhibition of glial cell migration by transducing signals in response to cell adhesion. Therefore, loss of PTPμ may contribute to the extensive dispersal of GBMs. The migration of brain tumor cells was assessed in vitro using a scratch wound assay. Parental U-87 MG cells express PTPμ and exhibited limited migration. However, short-hairpin RNA (shRNA)-mediated knockdown of PTPμ induced a morphological change and increased migration. Next, a brain slice assay replicating the three-dimensional environment of the brain was used. To assess migration, labeled U-87 MG glioma cells were injected into adult rat brain slices, and their movement was followed over time. Parental U-87 MG cells demonstrated limited dispersalrnin this assay. However, PTPμ shRNA induced migration and dispersal of U-87 MG cells in the brain slice. Finally, in a mouse xenograft model of intracranially injected U-87 MG cells, PTPμ shRNA induced morphological heterogeneity in these xenografts. Together, these data suggest that loss of PTPμ in human GBMs contributes to tumor cell migration and dispersal, implicating loss of PTPμ in glioma progression.
机译：细胞表面受体蛋白酪氨酸磷酸酶mu（PTPμ）是在CNS神经元和神经胶质细胞中表达的同型细胞粘附分子。胶质母细胞瘤（GBMs）是具有星形细胞相似性的最高级别的原发性脑肿瘤，其特征在于肿瘤细胞的明显扩散。在人GBM，低度星形细胞瘤和正常脑组织中检查了PTPμ表达。这些研究表明，与分散性较低的低级星形细胞瘤和正常大脑相比，高分散性GBM中PTPμ蛋白表达显着丧失。我们假设PTPμ通过转导响应细胞粘附的信号来促进神经胶质细胞迁移的接触抑制。因此，PTPμ的丢失可能有助于GBM的广泛扩散。使用刮伤试验在体外评估脑肿瘤细胞的迁移。亲本U-87 MG细胞表达PTPμ，并显示出有限的迁移。然而，短发夹RNA（shRNA）介导的PTPμ的敲低诱导了形态变化和增加的迁移。接下来，使用了复制大脑三维环境的大脑切片测定法。为了评估迁移，将标记的U-87 MG神经胶质瘤细胞注射到成年大鼠脑切片中，并随时间追踪其运动。亲本U-87 MG细胞在该试验中显示出有限的分散性。然而，PTPμshRNA诱导了U-87 MG细胞在脑切片中的迁移和扩散。最后，在颅内注射的U-87 MG细胞的小鼠异种移植模型中，PTPμshRNA诱导了这些异种移植的形态异质性。总之，这些数据表明，人GBM中PTPμ的丢失有助于肿瘤细胞迁移和扩散，这意味着神经胶质瘤进展中PTPμ的丢失。

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  • 来源
    《Neuro-Oncology》 |2009年第6期|767-778|共12页
  • 作者

    Adam M. Burgoyne; Juan M. Palomo; Polly J. Phillips-Mason; Susan M. Burden-Gulley; Denice L. Major; Anita Zaremba; Shenandoah Robinson; Andrew E. Sloan; Michael A. Vogelbaum; Robert H. Miller; Susann M. Brady-Kalnay;

  • 作者单位

    Department of Molecular Biology and Microbiology School of Medicine, Case Western Reserve University Cleveland, OH, USA;

    Department of Molecular Biology and Microbiology School of Medicine, Case Western Reserve University Cleveland, OH, USA Brain Tumor and Neuro-Oncology Center, Cleveland Clinic Foundation Cleveland, OH, USA;

    Department of Molecular Biology and Microbiology School of Medicine, Case Western Reserve University Cleveland, OH, USA;

    Department of Molecular Biology and Microbiology School of Medicine, Case Western Reserve University Cleveland, OH, USA;

    Department of Molecular Biology and Microbiology School of Medicine, Case Western Reserve University Cleveland, OH, USA;

    Department of Neurosciences School of Medicine, Case Western Reserve University Cleveland, OH, USA;

    Department of Neurosurgery School of Medicine, Case Western Reserve University Cleveland, OH, USA;

    Department of Neurosurgery School of Medicine, Case Western Reserve University Cleveland, OH, USA;

    Brain Tumor and Neuro-Oncology Center, Cleveland Clinic Foundation Cleveland, OH, USA;

    Department of Neurosciences School of Medicine, Case Western Reserve University Cleveland, OH, USA;

    Department of Molecular Biology and Microbiology School of Medicine, Case Western Reserve University Cleveland, OH, USA Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA;

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  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    cell migration; dispersal; glioblastoma; protein tyrosine phosphatase; PTPμ;

    机译：细胞迁移;分散胶质母细胞瘤蛋白酪氨酸磷酸酶;PTPμ;

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