Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Neuro Oncol. 2012 Oct;14(10):1254-64. doi: 10.1093/neuonc/nor202. Epub 2011 Dec 13.
For improvement of prognosis for glioblastoma patients, which remains poor, identification and targeting of glioblastoma progenitor cells are crucial. In this study, we found that the cluster of differentiation (CD)166/activated leukocyte cell adhesion molecule (ALCAM) was highly expressed on CD133+ glioblastoma progenitor cells. ALCAM+ CD133+ cells were highly enriched with tumor sphere-initiating cells in vitro. Among gliomas with isocitrate dehydrogenase-1/R132H mutation, the frequencies of ALCAM+ cells were significantly higher for glioblastomas than for World Health Organization grade II or III gliomas. The function of ALCAM in glioblastoma was then investigated. An in vitro invasion assay showed that transfection of ALCAM small interfering RNA or small hairpin RNA into glioblastoma cells significantly increased cell invasion without affecting cell proliferation. A soluble isoform of ALCAM (sALCAM) was also expressed in all glioblastoma samples and at levels that correlated well with ALCAM expression levels. In vitro invasion of glioblastoma cells was significantly enhanced by administration of purified sALCAM. Furthermore, overexpression of sALCAM in U87MG glioblastoma cells promoted tumor progression in i.c. transplants into immune-deficient mice. In summary, we were able to show that ALCAM constitutes a novel glioblastoma progenitor cell marker. We could also demonstrate that ALCAM and its soluble isoform are involved in the regulation of glioblastoma invasion and progression.
为了改善胶质母细胞瘤患者的预后（仍然很差），鉴定和靶向胶质母细胞瘤祖细胞至关重要。在这项研究中，我们发现分化群（CD）166/激活白细胞细胞黏附分子（ALCAM）在 CD133+胶质母细胞瘤祖细胞上高度表达。ALCAM+CD133+细胞在体外高度富集具有肿瘤球体起始细胞。在异柠檬酸脱氢酶-1/R132H 突变的胶质瘤中，ALCAM 细胞的频率对于胶质母细胞瘤明显高于世界卫生组织 II 级或 III 级胶质瘤。然后研究了 ALCAM 在胶质母细胞瘤中的功能。体外侵袭实验表明，ALCAM 小干扰 RNA 或短发夹 RNA 的转染显著增加了细胞侵袭，而不影响细胞增殖。可溶性 ALCAM（sALCAM）的同种型也在所有胶质母细胞瘤样本中表达，并且与 ALCAM 表达水平密切相关。纯化的 sALCAM 给药显著增强了胶质母细胞瘤细胞的体外侵袭。此外，sALCAM 在 U87MG 胶质母细胞瘤细胞中的过表达促进了免疫缺陷小鼠颅内移植中的肿瘤进展。总之，我们能够表明 ALCAM 构成了一种新型的胶质母细胞瘤祖细胞标志物。我们还可以证明 ALCAM 及其可溶性同种型参与了调节胶质母细胞瘤侵袭和进展。
