Sanchez-Martin Manuel
Department of Medicine, University of Salamanca, Campus Miguel de Unamuno s/n 37007 Salamanca, Spain.
Curr Stem Cell Res Ther. 2008 Sep;3(3):197-207. doi: 10.2174/157488808785740370.
The cancer relapse and mortality rate suggest that current therapies do not eradicate all malignant cells. Currently, it is accepted that tumorigenesis and organogenesis are similar in many respects, as for example, homeostasis is governed by a distinct sub-population of stem cells in both situations. There is increasing evidence that many types of cancer contain their own stem cells: cancer stem cells (CSC), which are characterized by their self-renewing capacity and differentiation ability. The investigation of solid tumour stem cells has gained momentum particularly in the area of brain tumours. Gliomas are the most common type of primary brain tumours. Nearly two-thirds of gliomas are highly malignant lesions with fast progression and unfortunate prognosis. Despite recent advances, two-year survival for glioblastoma (GBM) with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells endowed with features of primitive neural progenitor cells and a tumour-initiating function. In general, this fraction is characterized for forming neurospheres, being endowed with drug resistance properties and often, we can isolate some of them using sorting methods with specific antibodies. The molecular characterization of these stem populations will be critical to developing an effective therapy for these tumours with very dismal prognosis. To achieve this aim, the development of a mouse model which recapitulates the nature of these tumours is essential. This review will focus on glioma stem cell knowledge and discuss future implications in brain cancer therapy and regenerative medicine.
癌症复发率和死亡率表明,当前的治疗方法无法根除所有恶性细胞。目前,人们普遍认为肿瘤发生和器官发生在许多方面是相似的,例如,在这两种情况下,稳态均由特定的干细胞亚群控制。越来越多的证据表明,许多类型的癌症都含有自身的干细胞:癌症干细胞(CSC),其特征在于自我更新能力和分化能力。实体瘤干细胞的研究尤其在脑肿瘤领域获得了发展动力。神经胶质瘤是最常见的原发性脑肿瘤类型。近三分之二的神经胶质瘤是高度恶性病变,进展迅速且预后不佳。尽管最近取得了进展,但接受最佳治疗的胶质母细胞瘤(GBM)患者的两年生存率仍低于30%。即使在预后相对较好的低级别神经胶质瘤患者中,治疗也几乎无法治愈。最近的研究表明,存在一小部分具有原始神经祖细胞特征和肿瘤起始功能的神经胶质瘤细胞。一般来说,这部分细胞的特征是能够形成神经球,具有耐药性,而且我们常常可以使用特异性抗体分选方法分离出其中一些细胞。这些干细胞群体的分子特征对于开发针对这些预后极差的肿瘤的有效治疗方法至关重要。为实现这一目标,建立一个能够重现这些肿瘤本质的小鼠模型至关重要。本综述将聚焦于神经胶质瘤干细胞知识,并讨论其在脑癌治疗和再生医学中的未来意义。