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首页> 外文期刊>Cilia >Glioma cell proliferation is enhanced in the presence of tumor-derived cilia vesicles
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Glioma cell proliferation is enhanced in the presence of tumor-derived cilia vesicles

机译：在存在肿瘤来源的纤毛囊泡的情况下，胶质瘤细胞增殖得到增强

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The mechanisms by which primary cilia affect glioma pathogenesis are unclear. Depending on the glioma cell line, primary cilia can promote or inhibit tumor development. Here, we used piggyBac-mediated transgenesis to generate patient-derived glioblastoma (GBM) cell lines that stably express Arl13b:GFP in their cilia. This allowed us to visualize and analyze the behavior of cilia and ciliated cells during live GBM cell proliferation. Time-lapse imaging of Arl13b:GFP+ cilia revealed their dynamic behaviors, including distal tip excision into the extracellular milieu. Recent studies of non-cancerous cells indicate that this process occurs during the G0 phase, prior to cilia resorption and cell cycle re-entry, and requires ciliary recruitment of F-actin and actin regulators. Similarly, we observed ciliary buds associated with Ki67? cells as well as scattered F-actin+ cilia, suggesting that quiescent GBM cells may also utilize an actin network-based mechanism for ciliary tip excision. Notably, we found that the proliferation of ciliated GBM cells was promoted by exposing them to conditioned media obtained from ciliated cell cultures when compared to conditioned media collected from cilia-defective cell cultures (depleted in either KIF3A or IFT88 using CRISPR/Cas9). These results suggest that GBM cilia may release mitogenic vesicles carrying factors that promote tumor cell proliferation. Although Arl13b is implicated in tumor growth, our data suggest that Arl13b released from GBM cilia does not mediate tumor cell proliferation. Collectively, our results indicate that ciliary vesicles may represent a novel mode of intercellular communication within tumors that contributes to GBM pathogenesis. The mitogenic capacity of GBM ciliary vesicles and the molecular mediators of this phenomenon requires further investigation.
机译：原发性纤毛影响神经胶质瘤发病机制的机制尚不清楚。根据神经胶质瘤细胞系，原发性纤毛可以促进或抑制肿瘤的发展。在这里，我们使用了piggyBac介导的转基因来产生患者源性胶质母细胞瘤（GBM）细胞系，该细胞系在其纤毛中稳定表达Arl13b：GFP。这使我们能够可视化并分析活GBM细胞增殖过程中纤毛和纤毛细胞的行为。 Arl13b：GFP +纤毛的延时成像显示了它们的动态行为，包括末端尖端切除进入细胞外环境。对非癌细胞的最新研究表明，该过程发生在G0期，即纤毛吸收和细胞周期再进入之前，并且需要F-肌动蛋白和肌动蛋白调节剂的纤毛募集。同样，我们观察到与Ki67相关的睫状芽。细胞以及散布的F-肌动蛋白+纤毛，提示静止的GBM细胞也可能利用基于肌动蛋白网络的机制进行纤毛末端切除。值得注意的是，我们发现与通过纤毛缺损的细胞培养物收集的条件培养基（使用CRISPR / Cas9在KIF3A或IFT88中耗尽的条件培养基）相比，将纤毛的GBM细胞暴露于从纤毛细胞培养物获得的条件培养基中可以促进增殖。这些结果表明GBM纤毛可以释放有丝分裂的囊泡，其携带促进肿瘤细胞增殖的因子。尽管Arl13b与肿瘤的生长有关，但我们的数据表明从GBM纤毛释放的Arl13b不会介导肿瘤细胞的增殖。总的来说，我们的结果表明，睫状小泡可能代表了肿瘤内细胞间通讯的一种新模式，这有助于GBM发病机理。 GBM睫状小泡的促有丝分裂能力和这种现象的分子介质需要进一步研究。

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