Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells.
Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells.
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DOI：
10.1186/1471-2407-9-448
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发表时间：
2009-12-17
期刊：
影响因子：
3.8
通讯作者：
Rattner JB
中科院分区：
文献类型：
--
作者：
Moser JJ;Fritzler MJ;Rattner JB
初级纤毛是非运动的感觉细胞质细胞器，与信号转导、细胞间通讯、左右模式胚胎发育、流体流动感觉、钙水平调节、机械感觉、生长因子信号传导和细胞周期进程有关。这些结构的形成和/或功能缺陷是多种人类疾病的基础，例如 Alström、Bardet-Biedl、Joubert、Meckel-Gruber 和口腔-面部-数字 1 型综合征。初级纤毛在癌细胞中的表达和功能现已成为关注的焦点，但尚未在星形细胞瘤/胶质母细胞瘤中进行研究。为了开始解决这个问题，我们比较了正常人星形胶质细胞系与五种人星形细胞瘤/胶质母细胞瘤细胞系中初级纤毛的结构和表达。使用间接免疫荧光和电子显微镜检查培养的正常人星形胶质细胞和五种人星形细胞瘤/胶质母细胞瘤细胞系的初级纤毛表达和结构。使用单特异性抗体检测初级纤毛并绘制初级纤毛区域与内吞作用位点之间的关系。我们表明，正常星形胶质细胞中初级纤毛的表达与细胞周期相关，并且初级纤毛以独特的结构延伸穿过细胞，我们证明该结构是内吞作用的位点。重要的是，我们记录到，在五种星形细胞瘤/胶质母细胞瘤细胞系中，由于纤毛发生不完全，完全形成的初级纤毛要么以非常低的水平表达，要么完全不存在，要么具有异常形式。最近发现初级纤毛在多种细胞功能中的重要性，提出了这种结构可能在多种癌症中发挥作用的可能性。我们发现星形细胞瘤/胶质母细胞瘤来源的细胞中初级纤毛的形成受到破坏，这提供了第一个证据，证明初级纤毛表达和功能的改变可能是某些恶性表型的一部分。此外，我们提供了第一个证据表明纤毛发生不是一个全有或全无的过程。相反，缺陷可以在不同的点阻止这一过程，特别是在基体与质膜结合之后的阶段。
Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis. We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis. The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first evidence that altered primary cilium expression and function may be part of some malignant phenotypes. Further, we provide the first evidence that ciliogenesis is not an all or none process; rather defects can arrest this process at various points, particularly at the stage subsequent to basal body association with the plasma membrane.
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