Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA 90822, USA.
Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA 90095, USA.
Am J Transl Res. 2015 Feb 15;7(2):271-84. eCollection 2015.
Cancer cells derived from Glioblastoma multiforme possess membranous protrusions allowing these cells to infiltrate surrounding tissue, while resisting lymphocyte cytotoxicity. Microvilli and filopodia are supported by actin filaments cross-linked by fascin. Fascin-1 was genetically silenced within human U251 glioma cells; these knock-down glioma cells lost their microvilli/filopodia. The doubling time of these fascin-1 knock-down cells was doubled that of shRNA control U251 cells. Fascin-1 knock-down cells lost their transmigratory ability responding to interleukin-6 or insulin-like growth factor-1. Fascin-1 silenced U251 cells were more easily killed by cytolytic lymphocytes. Fascin-1 knock-down provides unique opportunities to augment glioma immunotherapy by simultaneously targeting several key glioma functions: like cell transmigration, cell division and resisting immune responses.
多形性胶质母细胞瘤衍生的癌细胞具有膜状突起，使这些细胞能够浸润周围组织，同时抵抗淋巴细胞的细胞毒性。微绒毛和丝状伪足由肌动蛋白丝支撑，肌动蛋白丝由 fascin 交联。在人 U251 神经胶质瘤细胞中， fascin-1 被基因沉默；这些敲低神经胶质瘤细胞失去了微绒毛/丝状伪足。这些 fascin-1 敲低细胞的倍增时间是 shRNA 对照 U251 细胞的两倍。 fascin-1 敲低细胞失去了对白细胞介素 6 或胰岛素样生长因子 1 的迁移能力。被细胞溶解淋巴细胞更容易杀死 fascin-1 沉默的 U251 细胞。 fascin-1 敲低为同时靶向几个关键的神经胶质瘤功能提供了独特的机会来增强神经胶质瘤的免疫治疗：如细胞迁移、细胞分裂和抵抗免疫反应。
