Tatenhorst L, Rescher U, Gerke V, Paulus W
Institute of Neuropathology, University Hospital Muenster, Muenster, Germany.
Neuropathol Appl Neurobiol. 2006 Jun;32(3):271-7. doi: 10.1111/j.1365-2990.2006.00720.x.
Diffuse invasion of brain tissue is a major reason for the poor prognosis of patients with glioblastoma. Annexin 2, a member of the large annexin family of Ca2+ and membrane-binding proteins, is expressed at high protein levels in human gliomas and has been proposed as a marker of glioma malignancy, while its functional role in these tumours is unknown so far. The ability of annexin 2 to interact with the actin cytoskeleton, as well as its potential to bind invasion-associated proteases, suggests that it could participate in invasion-associated processes in human gliomas. Therefore, we analysed here functional consequences of RNA interference-mediated silencing of annexin 2 in U87MG and U373MG human glioma cell lines. While no impact of annexin 2 downregulation on proliferation and adhesion was observed, our analyses revealed that migration of U87MG and U373MG cells was significantly inhibited following annexin 2 depletion. This effect was not related to a compensatory increase of the related annexins 1 or 6. Our findings identify annexin 2 as a potential candidate involved in glioma invasion and support the potential of RNA interference as powerful tool in the decryption of glioma invasion mechanisms.
脑组织的弥漫性浸润是胶质母细胞瘤患者预后不良的主要原因。膜联蛋白2是Ca2+和膜结合蛋白的大型膜联蛋白家族的成员之一，在人类胶质瘤中以高蛋白水平表达，并已被提议作为胶质瘤恶性程度的标志物，但其在这些肿瘤中的功能作用迄今尚不清楚。膜联蛋白2与肌动蛋白细胞骨架相互作用的能力，以及其结合侵袭相关蛋白酶的潜力，表明它可能参与人类胶质瘤的侵袭相关过程。因此，我们在此分析了RNA干扰介导的U87MG和U373MG人胶质瘤细胞系中膜联蛋白2沉默的功能后果。虽然未观察到膜联蛋白2下调对增殖和黏附的影响，但我们的分析显示，膜联蛋白2缺失后，U87MG和U373MG细胞的迁移受到显著抑制。这种效应与相关膜联蛋白1或6的代偿性增加无关。我们的研究结果确定膜联蛋白2是参与胶质瘤侵袭的潜在候选物，并支持RNA干扰作为解密胶质瘤侵袭机制的有力工具的潜力。
