肿瘤干细胞在实体肿瘤放射治疗中的意义

Significance of tumor stem cells in radiotherapy for solid tumor

在肿瘤形成学说中有随机学说与阶层学说两种。阶层学说认为肿瘤起源细胞即为肿瘤干细胞。在白细胞以及部分实体肿瘤中的一小部分肿瘤细胞具有无限增殖的能力,并可形成新的肿瘤灶,称之为肿瘤干细胞。肿瘤干细胞是肿瘤转移、复发的根源。肿瘤是干细胞长期自我更新过程中,由于多基因突变导致其生长失去了正常调控而停止在分化的某一阶段无限制增殖所形成,所处的微环境通过某些信号通道以及分泌多种细胞因子来发挥调控作用,而微环境的改变致使干细胞的分化方向发生改变可能是肿瘤发生的基础。目前,利用细胞不同表面抗原标记及侧群细胞分选是肿瘤干细胞分选的两种常用方法。侧群细胞分选更为方便、经济,并可表面标记未知肿瘤干细胞的分选。肿瘤干细胞的鉴定只能用功能学方法,即对其自我更新能力与分化潜能两个主要特征进行评价。肿瘤干细胞放射抗拒的机制可能与损伤DNA的修复,影响细胞周期调控、细胞凋亡、增殖等转导通路改变有关。将肿瘤干细胞作为放射治疗的切入点,针对其放射生物学行为制订对策,才能从根本上解决问题。

Tumorigenesis theory contains stochastic theory and hierarchy. Hierarchy believes that cancer-initiating cells are tumor stem cells, A small quantity of tumor cells in leukocytes and some sohd tumors possess the ability to infinite proliferation and form new tumor focus, which is called tumor stem cells. Tumor stem cells are the root of tumor metastasis and recurrence. Tumor appears during self-renewal of stem cells when stem cells infinitely proliferate induced by gene mutation. Microenvironment exhibits a regulatory effect by some Signal passageways and secreting varied cytokines, Changes in differentiation of stem cells induced by microenvironment may be a cause of tumorigenesis. Presently, different surface antigen labeling and side population cell sorting are common methods of tumor stem cell sorting. The side population cell sorting is more convenient, and can label unknown tumor stem cell sorting. Tumor stem cells only can be identified by function method; that is, to assess the ability of self-renewal and differentiation. Radioresistant mechanism of tumor stem cells may be associated with the recovery of DNA injury, cell cycle regulation, cell apoptosis and proliferation. Taking radiotherapy of tumor stem cells as a contact point, strategy designed by radiobiology can essentially solve this problem.