Fomchenko Elena I, Holland Eric C
Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Exp Cell Res. 2005 Jun 10;306(2):323-9. doi: 10.1016/j.yexcr.2005.03.007. Epub 2005 Apr 14.
One of the most devastating CNS pathologies is brain cancer. The undifferentiated character of brain tumor cells and recent reports of cancer stem cells prompt questions regarding the involvement of normal stem/progenitor cells in brain tumor biology, their potential contribution to the tumor itself, and whether they are the cause or the consequence of tumor initiation and progression. The cancer stem cell model proposes a clonally derived brain tumor arising from a cancer stem cell. This tumor cell-of-origin originates from a stem/progenitor or more differentiated cell via acquisition of oncogenic mutations that dysregulate or allow reacquisition of self-renewal mechanisms. The tumor cells differentiate unidirectionally from the cancer stem cell in a way parallel to normal development. However, several properties of brain tumors add complexity to this model. For example, the apparent lineage and differentiation status of tumor cells are significantly affected by signaling abnormalities that are causally related to formation of the tumor. In addition, these tumors recruit normal CNS stem and progenitor cells to the tumor mass leading to the possibility of a heterogeneous and polyclonal cell population. It is likely that a complete description of the role of stem cells in brain tumors will be more complex than our current models.
最具毁灭性的中枢神经系统病理学疾病之一是脑癌。脑肿瘤细胞的未分化特性以及近期有关癌症干细胞的报道引发了诸多问题，涉及正常干细胞/祖细胞在脑肿瘤生物学中的作用、它们对肿瘤本身的潜在贡献，以及它们是肿瘤起始和进展的原因还是结果。癌症干细胞模型提出，克隆起源的脑肿瘤源自癌症干细胞。这种肿瘤起源细胞通过获得致癌突变而从干细胞/祖细胞或更分化的细胞产生，这些突变会失调或使自我更新机制重新获得。肿瘤细胞从癌症干细胞单向分化，其方式与正常发育平行。然而，脑肿瘤的几个特性使该模型变得复杂。例如，肿瘤细胞的明显谱系和分化状态会受到与肿瘤形成有因果关系的信号异常的显著影响。此外，这些肿瘤会将正常的中枢神经系统干细胞和祖细胞募集到肿瘤块中，导致细胞群体可能具有异质性和多克隆性。干细胞在脑肿瘤中的作用的完整描述可能比我们目前的模型更为复杂。
