Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy.
Stem Cells. 2013 May;31(5):857-69. doi: 10.1002/stem.1317.
The role of the cell surface CD133 as a cancer stem cell marker in glioblastoma (GBM) has been widely investigated, since it identifies cells that are able to initiate neurosphere growth and form heterogeneous tumors when transplanted in immune-compromised mice. However, evidences of CD133-negative cells exhibiting similar properties have also been reported. Moreover, the functional role of CD133 in cancer stem/progenitor cells remains poorly understood. We studied the biological effects of CD133 downregulation in GBM patient-derived neurospheres. Our results indicate that there is not a hierarchical relation between CD133-positive and CD133-negative cells composing the neurospheres. Indeed, CD133 appears in an interconvertible state, changing its subcellular localization between the cytoplasm and the plasmamembrane of neurosphere cells. Silencing of CD133 in human GBM neurospheres using lentivirus-mediated short hairpin RNA impairs the self-renewal and tumorigenic capacity of neurosphere cells. These results imply that CD133 could be used as a therapeutic target in GBMs.
细胞表面 CD133 作为神经胶质瘤（GBM）中的癌症干细胞标志物的作用已被广泛研究，因为它可以识别出能够启动神经球生长并在免疫缺陷小鼠中移植时形成异质性肿瘤的细胞。然而，也有报道称 CD133 阴性细胞具有类似的特性。此外，CD133 在癌症干细胞/祖细胞中的功能作用仍知之甚少。我们研究了下调 GBM 患者来源的神经球中的 CD133 对其生物学效应。我们的结果表明，组成神经球的 CD133 阳性和 CD133 阴性细胞之间没有等级关系。事实上，CD133 处于可转换状态，在神经球细胞的细胞质和质膜之间改变其亚细胞定位。使用慢病毒介导的短发夹 RNA 沉默人 GBM 神经球中的 CD133 会损害神经球细胞的自我更新和致瘤能力。这些结果表明 CD133 可作为 GBM 的治疗靶点。
