Mitochondrial Network in Glioma's Invadopodia Displays an Activated State Both in Situ and in Vitro: Potential Functional Implications
Mitochondrial Network in Glioma's Invadopodia Displays an Activated State Both in Situ and in Vitro: Potential Functional Implications
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DOI：
10.3109/01913123.2012.694582
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发表时间：
2012-12-01
影响因子：
1
通讯作者：
Jadus, Martin R.
中科院分区：
文献类型：
--
作者：
Arismendi-Morillo, Gabriel;Hoa, Neil T.;Jadus, Martin R.
胶质瘤的典型特征是浸润性，其预后与肿瘤细胞的浸润性有关。多形性胶质母细胞瘤是一种侵袭性很强的癌症，这导致了其致死率。内过足被认为对它们的运动性至关重要。用透射电子显微镜和免疫荧光显微镜对人胶质瘤细胞侵足进行了观察。电镜下，原位胶质瘤（原纤维星形细胞瘤、间变性星形细胞瘤、多形性胶质母细胞瘤、毛细胞星形细胞瘤）显示线粒体具有致密基质凝聚结构，表明其处于活跃状态。线粒体经常与延伸的光滑内质网密切接触，显示与线粒体相关的内质网亚段。丝状足内可见线粒体，线粒体穿透细胞外基质。在与微血管相关的侵殖体内也检测到活化的线粒体和光滑的内质网。荧光显微镜证实，体外生长的D54和U251胶质瘤细胞也含有带线粒体的丝状足。U251胶质瘤细胞的丝状伪足穿过1.2 μ m的transwell腔室孔，也含有线粒体，表明线粒体积极参与了侵袭过程。肿瘤细胞的迁移和侵袭需要细胞运动性的增加，并涉及板足、质膜突起和单个丝状足[1]的形成。胶质瘤的典型特征是其浸润性，导致肿瘤和正常脑组织之间界限不清。其不良预后可能与这些细胞的侵袭性有关。这些肿瘤细胞的运动性与侵过足[2]的存在有关，因此，对其结构和分子方面有更多的了解是必要的。有证据表明，胶质母细胞瘤多形性细胞具有强大的侵入性活性[3,4]。由于侵入性足在肿瘤事件（如细胞侵袭和基质降解）中的重要影响，需要对其结构和分子方面有更多的了解。入侵足的动态组装仍未被很好地理解，线粒体结构和功能的改变对细胞移动的影响也知之甚少。本文描述了我们最近观察到的胶质瘤侵入足内线粒体网络的两个突出结构特征。我们相信这两个特征（激活的线粒体和光滑的内质网，以及丝状足内的线粒体）可能为研究人员提供未来控制胶质瘤侵袭性治疗的可能靶点。
Gliomas are typically characterized by their infiltrative nature, and the prognosis can be linked to the invasive nature of the tumoral cells. Glioblastoma multiforme are very invasive cancers and this contributes to their lethality. The invadopodia are considered essential for their motility. Human glioma cell invadopodia were examined with transmission electron and immunofluorescent microscopy. By electron microscopy, in situ gliomas (fibrillary astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, pilocytic astrocytoma) show mitochondria with a dense matrix condensed configuration, indicating an active state. The mitochondria were frequently in close contact with an extended smooth endoplasmic reticulum displaying an endoplasmic reticulum subfraction associated with mitochondria. Mitochondria were seen within the filopodia that were penetrating into the extracellular matrix. The activated mitochondria and smooth endoplasmic reticulum were also detected within the invadopdia, which was associated microblood vessels. Fluorescent microscopy confirmed that D54 and U251 glioma cells growing in vitro also contained filopodia with mitochondria. The U251 glioma cells' filopodia that penetrated through 1.2-mu m pores of transwell chambers also contained mitocondria, suggesting that the mitochondria are actively involved in the invasion process.Migration and invasion of tumor cells requires an increase in cellular motility and involves formation of lamellipodia, protrusions of the plasma membrane, and individual filopodia [1]. Gliomas are typically characterized by their infiltrative nature, resulting in a poorly demarcated interface between tumor and normal brain tissue. Their poor prognosis can be linked to the invasive nature of these cells. The motility of these tumor cells is correlated with the presence of invadopodia [2], and, consequently, more insight is necessary into their structural and molecular aspects. Evidence of robust invadopodia activity in glioblastoma multiforme cells has been reported [3,4].Because of the significant impact of invadopodia in oncological events such as cell invasion and matrix degradation, more insight into structural and molecular aspects is needed [2]. The dynamic assembly of invadopodia is still not well understood [2], and little is known of the alterations in mitochondrial structure and function that contribute to cell mobility [5]. This paper describes two prominent structural features of the mitochondrial network present within the glioma's invadopodia that we have recently observed. We believe these two features (activated mitochondria and smooth ER, along with mitochondria contained within the filopodia) might provide researchers with possible targets for future therapies that can control glioma invasiveness.