Arismendi-Morillo Gabriel, Hoa Neil T, Ge Lisheng, Jadus Martin R
Biological Research Institute, University of Zulia, Maracaibo, Venezuela.
Ultrastruct Pathol. 2012 Dec;36(6):409-14. doi: 10.3109/01913123.2012.694582.
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-μm 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.
胶质瘤通常以其浸润性为特征，其预后可能与肿瘤细胞的侵袭性有关。多形性胶质母细胞瘤是极具侵袭性的癌症，这也是其致死率高的原因之一。侵袭伪足被认为对其运动至关重要。我们通过透射电子显微镜和免疫荧光显微镜对人胶质瘤细胞的侵袭伪足进行了研究。通过电子显微镜观察发现，原位胶质瘤（纤维型星形细胞瘤、间变性星形细胞瘤、多形性胶质母细胞瘤、毛细胞型星形细胞瘤）中的线粒体呈现出基质致密浓缩的形态，表明其处于活跃状态。线粒体经常与延伸的光滑内质网紧密接触，显示出与线粒体相关的内质网亚组分。在伸入细胞外基质的丝状伪足内可见线粒体。在与微血管相关的侵袭伪足内也检测到了活化的线粒体和光滑内质网。荧光显微镜证实，体外培养的D54和U251胶质瘤细胞也含有带有线粒体的丝状伪足。穿透Transwell小室1.2μm孔径的U251胶质瘤细胞的丝状伪足也含有线粒体，这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增强，涉及片状伪足、质膜突起和单个丝状伪足的形成[1]。胶质瘤通常以其浸润性为特征，导致肿瘤与正常脑组织之间的界限不清。其预后不良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袭伪足的存在相关[2]，因此，有必要对其结构和分子方面进行更深入的研究。已有报道多形性胶质母细胞瘤细胞中存在强大的侵袭伪足活性[3,4]。由于侵袭伪足在诸如细胞侵袭和基质降解等肿瘤学事件中具有重大影响，因此需要对其结构和分子方面进行更深入的了解[2]。侵袭伪足的动态组装仍未得到很好的理解[2]，对于有助于细胞迁移的线粒体结构和功能的改变知之甚少[5]。本文描述了我们最近在胶质瘤侵袭伪足内观察到的线粒体网络的两个突出结构特征。我们认为这两个特征（活化的线粒体和光滑内质网，以及丝状伪足内包含的线粒体）可能为研究人员提供未来控制胶质瘤侵袭性治疗的潜在靶点。
