Center for Experimental Research, The First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Biochem Biophys Res Commun. 2011 Mar 25;406(4):643-8. doi: 10.1016/j.bbrc.2011.02.123. Epub 2011 Mar 1.
Glioblastomas (GBMs) are the most lethal and common types of primary brain tumors. The hallmark of GBMs is their highly infiltrative nature. The cellular and molecular mechanisms underlying the aggressive cancer invasion in GBMs are poorly understood. GBM displays remarkable cellular heterogeneity and hierarchy containing self-renewing glioblastoma stem cells (GSCs). Whether GSCs are more invasive than non-stem tumor cells and contribute to the invasive phenotype in GBMs has not been determined. Here we provide experimental evidence supporting that GSCs derived from GBM surgical specimens or xenografts display greater invasive potential in vitro and in vivo than matched non-stem tumor cells. Furthermore, we identified several invasion-associated proteins that were differentially expressed in GSCs relative to non-stem tumor cells. One of such proteins is L1CAM, a cell surface molecule shown to be critical to maintain GSC tumorigenic potential in our previous study. Immunohistochemical staining showed that L1CAM is highly expressed in a population of cancer cells in the invasive fronts of primary GBMs. Collectively, these data demonstrate the invasive nature of GSCs, suggesting that disrupting GSCs through a specific target such as L1CAM may reduce GBM cancer invasion and tumor recurrence.
胶质母细胞瘤（GBM）是最致命和最常见的原发性脑肿瘤。GBM 的标志是其高度浸润性。GBM 中侵袭性癌症侵袭的细胞和分子机制尚未完全了解。GBM 表现出明显的细胞异质性和层次结构，包含自我更新的胶质母细胞瘤干细胞（GSCs）。GSCs 是否比非干细胞肿瘤细胞更具侵袭性，并有助于 GBM 中的侵袭表型尚未确定。在这里，我们提供了实验证据，支持源自 GBM 手术标本或异种移植物的 GSCs 在体外和体内比匹配的非干细胞肿瘤细胞具有更大的侵袭潜力。此外，我们鉴定了一些在 GSCs 中相对于非干细胞肿瘤细胞差异表达的侵袭相关蛋白。其中一种蛋白是 L1CAM，是我们之前的研究中表明对维持 GSC 肿瘤发生潜能至关重要的细胞表面分子。免疫组织化学染色显示，L1CAM 在原发性 GBM 侵袭前沿的一群癌细胞中高度表达。总之，这些数据表明 GSCs 具有侵袭性，表明通过 L1CAM 等特定靶标破坏 GSCs 可能会降低 GBM 癌症侵袭和肿瘤复发的风险。
