Colin C, Baeza N, Bartoli C, Fina F, Eudes N, Nanni I, Martin P-M, Ouafik L, Figarella-Branger D
Laboratoire de Biopathologie de l'Adhésion et de la Signalisation, EA3281, IPHM, Faculté de Médecine Timone, 13005, Marseille, France.
Oncogene. 2006 May 4;25(19):2818-26. doi: 10.1038/sj.onc.1209305.
Glioblastoma (GBM) is a highly malignant glioma, which has the propensity to infiltrate throughout the brain in contrast to pilocytic astrocytoma (PA) of the posterior fossa, which does not spread and can be cured by surgery. We have used Suppression Subtractive Hybridization to define markers that better delineate the molecular basis of brain invasion and distinguish these tumor groups. We have identified 106 genes expressed in PA versus GBM and 80 genes expressed in GBM versus PA. Subsequent analysis identified a subset of 20 transcripts showing a common differential expression pattern for the two groups. GBM differs from PA by the expression of five genes involved in invasion and angiogenesis: fibronectin, osteopontin, chitinase-3-like-1 (YKL-40), keratoepithelin and fibromodulin. PA differs from GBM by the expression of genes related to metabolism (apolipoprotein D), proteolysis (protease-serine-11), receptor and signal transduction (PLEKHB1 for Pleckstrin-Homology-domain-containing-protein-family-B-member-1), transcription/translation (eukaryotic-translation-elongation-factor-1-alpha1) processes and cell adhesion (SPOCK1 for SPARC/Osteonectin-CWCV-kazal-like-domains-proteoglycan). The expression of these genes was confirmed by real-time quantitative RT-PCR and immunohistochemistry. This study highlights the crucial role of brain invasion in GBM and identifies specific molecules involved in this process. In addition, it offers a restricted list of markers that accurately distinguish PA from GBM.
胶质母细胞瘤（GBM）是一种高度恶性的胶质瘤，与后颅窝的毛细胞型星形细胞瘤（PA）不同，它易于在整个大脑中浸润，而后颅窝的毛细胞型星形细胞瘤不会扩散，可通过手术治愈。我们利用抑制性消减杂交技术来确定能更好地描绘脑侵袭分子基础并区分这些肿瘤组别的标志物。我们鉴定出了在PA与GBM中表达的106个基因以及在GBM与PA中表达的80个基因。随后的分析确定了20个转录本的一个子集，其显示出两组共有的差异表达模式。GBM与PA的不同之处在于参与侵袭和血管生成的五个基因的表达：纤连蛋白、骨桥蛋白、几丁质酶-3样-1（YKL-40）、角化上皮蛋白和纤维调节蛋白。PA与GBM的不同之处在于与代谢（载脂蛋白D）、蛋白水解（丝氨酸蛋白酶-11）、受体和信号转导（含Pleckstrin同源结构域蛋白家族B成员1的PLEKHB1）、转录/翻译（真核翻译延伸因子-1-α1）过程以及细胞黏附（富含半胱氨酸的酸性分泌蛋白/骨连接蛋白-CWCV- Kazal样结构域蛋白聚糖的SPOCK1）相关的基因的表达。这些基因的表达通过实时定量逆转录-聚合酶链反应和免疫组织化学得以证实。本研究突出了脑侵袭在GBM中的关键作用，并鉴定出了参与这一过程的特定分子。此外，它提供了一份有限的标志物清单，可准确区分PA与GBM。
