Tso Cho-Lea, Shintaku Peter, Chen James, Liu Qinghai, Liu Jason, Chen Zugen, Yoshimoto Koji, Mischel Paul S, Cloughesy Timothy F, Liau Linda M, Nelson Stanley F
Department of Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, Room 5506, 695 Young Drive South, Los Angeles, CA 90095, USA.
Mol Cancer Res. 2006 Sep;4(9):607-19. doi: 10.1158/1541-7786.MCR-06-0005.
Glioblastoma is the most common and aggressive primary brain cancer. Recent isolation and characterization of brain tumor-initiating cells supports the concept that transformed neural stem cells may seed glioblastoma. We previously identified a wide array of mesenchymal tissue transcripts overexpressed in a broad set of primary glioblastoma (de novo) tumors but not in secondary glioblastoma (derived from lower-grade) tumors, low-grade astrocytomas, or normal brain tissues. Here, we extend this observation and show that a subset of primary glioblastoma tumors and their derived tumor lines express cellular and molecular markers that are associated with mesenchymal stem cells (MSC) and that glioblastoma cell cultures can be induced to differentiate into multiple mesenchymal lineage-like cell types. These findings suggest either that a subset of primary glioblastomas derive from transformed stem cells containing MSC-like properties and retain partial phenotypic aspects of a MSC nature in tumors or that glioblastomas activate a series of genes that result in mesenchymal properties of the cancer cells to effect sustained tumor growth and malignant progression.
胶质母细胞瘤是最常见且侵袭性最强的原发性脑癌。近期对脑肿瘤起始细胞的分离和特性分析支持了转化神经干细胞可能是胶质母细胞瘤起源的观点。我们之前在大量原发性胶质母细胞瘤(新发)肿瘤中发现了一系列过表达的间充质组织转录本,但在继发性胶质母细胞瘤(由低级别肿瘤衍生而来)、低级别星形细胞瘤或正常脑组织中未发现。在此,我们扩展了这一观察结果,并表明一部分原发性胶质母细胞瘤肿瘤及其衍生的肿瘤细胞系表达与间充质干细胞(MSC)相关的细胞和分子标志物,且胶质母细胞瘤细胞培养物可被诱导分化为多种间充质谱系样细胞类型。这些发现表明,要么一部分原发性胶质母细胞瘤源自具有类似MSC特性的转化干细胞,并在肿瘤中保留了MSC性质的部分表型特征,要么胶质母细胞瘤激活了一系列导致癌细胞具有间充质特性的基因,以实现肿瘤的持续生长和恶性进展。