Detection of primary cilia in human glioblastoma.
Detection of primary cilia in human glioblastoma.
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DOI：
10.1007/s11060-013-1340-y
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发表时间：
2014-03
影响因子：
3.9
通讯作者：
Reynolds, Brent A.
中科院分区：
文献类型：
--
作者：
Sarkisian, Matthew R.;Siebzehnrubl, Dorit;Lan Hoang-Minh;Deleyrolle, Loic;Silver, Daniel J.;Siebzehnrubl, Florian A.;Guadiana, Sarah M.;Srivinasan, Gayathri;Semple-Rowland, Susan;Harrison, Jeffrey K.;Steindler, Dennis A.;Reynolds, Brent A.
胶质母细胞瘤（GBM）是最常见的恶性成人脑肿瘤，由于原发性和获得性耐药而预后不良。虽然 GBM 的许多细胞特征已被记录，但尚不清楚这些肿瘤内的细胞是否延伸初级纤毛，初级纤毛是一种细胞器，其相关信号通路可能调节神经前体细胞和肿瘤细胞的增殖、迁移和存活。使用免疫组织化学和电子显微镜 (EM) 技术，我们筛选了人类 GBM 肿瘤活检和原代细胞系中的纤毛。五个原代 GBM 细胞系的免疫细胞化学染色显示，每个细胞系中 8% 至 25% 的细胞具有 γ 微管蛋白阳性基体，从中延伸出乙酰化的 α 微管蛋白阳性轴丝。电镜分析证实了细胞表面纤毛的存在，并揭示了它们的轴丝包含有组织的微管网络，这一结构特征与我们沿轴丝长度检测到的两种贩运纤毛蛋白 IFT88 和 Arl13b 一致。值得注意的是，在检查的 23 个肿瘤活检组织（22 个原发肿瘤和 1 个复发肿瘤）中均检测到纤毛。这些纤毛分布在整个肿瘤区域，包括靠近脉管系统的区域和坏死区域内。此外，这些肿瘤内的纤毛细胞与 Ki67（一种活跃分裂细胞的标记物）和 ZEB1（一种在 GBM 中上调并与肿瘤发生、侵袭和化疗耐药相关的转录因子）共染色。总的来说，我们的数据表明人类 GBM 肿瘤内的细胞亚群有纤毛。鉴于越来越多的证据支持原发纤毛在肿瘤发生和传播中的作用，进一步研究纤毛对GBM肿瘤细胞功能的影响可能会提高我们对GBM发病机制的理解，并可能为GBM治疗策略提供新的方向。
Glioblastoma (GBM) is the most common malignant adult brain tumor and carries a poor prognosis due to primary and acquired resistance. While many cellular features of GBM have been documented, it is unclear if cells within these tumors extend a primary cilium, an organelle whose associated signaling pathways may regulate proliferation, migration, and survival of neural precursor and tumor cells. Using immunohistochemical and electron microscopy (EM) techniques, we screened human GBM tumor biopsies and primary cell lines for cilia. Immunocytochemical staining of five primary GBM cell lines revealed that between 8 and 25 % of the cells in each line possessed gamma tubulin-positive basal bodies from which extended acetylated, alpha-tubulin-positive axonemes. EM analyses confirmed the presence of cilia at the cell surface and revealed that their axonemes contained organized networks of microtubules, a structural feature consistent with our detection of IFT88 and Arl13b, two trafficked cilia proteins, along the lengths of the axonemes. Notably, cilia were detected in each of 23 tumor biopsies (22 primary and 1 recurrent) examined. These cilia were distributed across the tumor landscape including regions proximal to the vasculature and within necrotic areas. Moreover, ciliated cells within these tumors co-stained with Ki67, a marker for actively dividing cells, and ZEB1, a transcription factor that is upregulated in GBM and linked to tumor initiation, invasion, and chemoresistance. Collectively, our data show that subpopulations of cells within human GBM tumors are ciliated. In view of mounting evidence supporting roles of primary cilia in tumor initiation and propagation, it is likely that further study of the effects of cilia on GBM tumor cell function will improve our understanding of GBM pathogenesis and may provide new directions for GBM treatment strategies.
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影响因子：
3.8
作者：
Moser JJ;Fritzler MJ;Rattner JB
通讯作者：
Rattner JB
影响因子：
56.9
作者：
Rohatgi, Rajat;Milenkovic, Ljiljana;Scott, Matthew P.
通讯作者：
Scott, Matthew P.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.bbrc.2010.09.081
发表时间：
2010-10-22
影响因子：
3.1
作者：
Chakravarthy, Balu;Gaudet, Chantal;Whitfield, James
通讯作者：
Whitfield, James
DOI：
10.1073/pnas.0804558105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Breunig, Joshua J.;Sarkisian, Matthew R.;Town, Terrence
通讯作者：
Town, Terrence