Establishment of a Human Grade IV Glioma Stem Cell Line Bank

描述(申请人提供)：胶质母细胞瘤(GB)是最常见的成人原发脑肿瘤，预后很差，这在很大程度上归因于组成肿瘤的细胞的极端异质性、分子和遗传变化的持续进化，以及因此肿瘤对传统治疗的耐药性。除手术切除外，实体组织肿瘤患者的主要治疗方法是全身应用细胞毒性化合物。传统上，人脑胶质瘤是在高浓度血清作为贴壁培养物存在的情况下体外生长的。虽然这些血清培养物可以在很长一段时间内保持，并且由此产生的后代在动物模型中是致瘤的，但它们没有显示出许多在原发肿瘤中看到的明确的表型特征。最近，用于分离、扩增和研究神经干细胞的神经球试验[NSA]的应用已被应用于GB。在这些条件下，可以在特定的条件下产生GB细胞系，重要的是在培养的细胞移植后；由此产生的肿瘤表现出典型的人类GB的体内特征；概括了原代GBM的形态、基因和基因表达模式，以及广泛的迁移和渗透能力。因此，NSA在GB研究中的应用可能为胶质瘤生物学研究提供一个更具生物学意义的模型系统，并可能被用于新的治疗药物的鉴定。目前，还没有商业来源的NSA分离的GB细胞系已经广泛地表征了[体外和体内]的表型和基因组学特征。在这项申请中，我们提议分离并储存50条这样的患者来源的线路，并将其提供给研究社区。

DESCRIPTION (provided by applicant): Glioblastoma (GB) is the most common primary brain tumor in adults and has a dismal prognosis, which is attributed largely to extreme heterogeneity in the cells that make up the cancer, continual evolution of molecular and genetic alterations, and thus resistance of the tumor to conventional treatments. Beyond surgical resection, systemic treatment with cytotoxic compounds is the main treatment for patients with solid tissue tumors. Traditionally, human glioma tumors have been grown ex vivo in the presence of high concentrations of serum as adherent cultures. While these serum grown cultures can be maintained for extensive periods of time and the resulting progeny are tumorigenic in animal models, they do not display many of the defining phenotypic features that are seen in the primary tumor. Recently, application of the Neurosphere Assay [NSA], which has been used to isolate, expand and study neural stem cells, has been applied to GB. Under these conditions, GB cell lines can be generated under defined conditions and importantly following implantation of the cultured cells; the resulting tumors exhibit the classic in vivo features of human GB; recapitulating the morphology, genotype and gene expression patterns of primary GBMs, as well as having extensive migratory and infiltrative capacity. Hence, application of the NSA to the study of GB may provide a more biologically relevant model system for studying glioma biology and maybe exploited for identification of new therapeutic agents. Currently there are no commercial sources of NSA isolated GB cell lines that have been extensively characterized both phenotypically [in vitro and in vivo] and genomically. Within this application we are proposing to isolate and bank 50 such patient derived lines and make them available to the research community.