Kühnöl Caspar D, Würfel Carina, Staege Martin S, Kramm Christof
Department of Pediatrics, University Clinic and Polyclinic for Child and Adolescent Medicine I, Martin Luther University Halle-Wittenberg, D-06120 Halle, Germany.
Division of Pediatric Hematology and Oncology, Department of Child and Adolescent Health, Georg August University Göttingen, D-37075 Göttingen, Germany.
Oncol Lett. 2017 May;13(5):3882-3888. doi: 10.3892/ol.2017.5875. Epub 2017 Mar 17.
Despite advancements in neurosurgery, chemotherapy and radiation therapy, the outcome of patients with glioblastoma remains poor. The migration of tumor cells from the primary tumor site with subsequent invasion of these cells into the surrounding normal brain tissue is frequently responsible for relapse and treatment failure. The present study hypothesized that snail homolog 1 (SNAI1), a factor critically involved in the epithelial-mesenchymal transition (EMT) of human carcinoma cells, may also contribute to an invasive EMT-like phenotype of glioblastoma cells. The majority of glioblastoma cell lines investigated in the present study expressed SNAI1 at basal levels. The present study overexpressed SNAI1 in glioblastoma cell lines by lentiviral transfer of human SNAI1 complementary DNA. In addition, the inhibition of SNAI1 expression was achieved by lentiviral transfer of a short hairpin RNA specific for SNAI1. SNAI1 overexpression increased proliferation of one of the cell lines, U251MG, but exhibited only a weak effect on the migration and invasion of glioblastoma cells. However, downregulation of SNAI1 significantly decreased the invasive capacity of all investigated cell lines. In parallel, regained expression of E-cadherin, a marker that is usually lost during EMT, was observed subsequent to SNAI1 knockdown in the glioblastoma cell lines U87MG and U251MG. The data of the present study suggest that certain key genes of the EMT in carcinoma are also involved in the migration and invasion of human glioblastoma cells.
尽管神经外科手术、化疗和放射治疗取得了进展,但胶质母细胞瘤患者的预后仍然很差。肿瘤细胞从原发肿瘤部位迁移并随后侵入周围正常脑组织,这常常导致复发和治疗失败。本研究假设,蜗牛同源物1(SNAI1),一种在人类癌细胞上皮-间质转化(EMT)中起关键作用的因子,可能也有助于胶质母细胞瘤细胞呈现侵袭性的EMT样表型。本研究中调查的大多数胶质母细胞瘤细胞系在基础水平表达SNAI1。本研究通过慢病毒介导的人SNAI1互补DNA转染,在胶质母细胞瘤细胞系中过表达SNAI1。此外,通过慢病毒介导的针对SNAI1的短发夹RNA转染来抑制SNAI1表达。SNAI1过表达增加了其中一个细胞系U251MG的增殖,但对胶质母细胞瘤细胞的迁移和侵袭仅表现出微弱影响。然而,SNAI1的下调显著降低了所有研究细胞系的侵袭能力。同时,在胶质母细胞瘤细胞系U87MG和U251MG中,SNAI1敲低后观察到E-钙黏蛋白(一种在EMT过程中通常会丢失的标志物)的表达恢复。本研究数据表明,癌中EMT的某些关键基因也参与了人类胶质母细胞瘤细胞的迁移和侵袭。