Piccirillo Sara G M, Vescovi Angelo L
University of Milan, Department of Biotechnology and Biosciences, Bicocca & Stemgen, SPA, Milan, Italy.
Expert Opin Biol Ther. 2007 Aug;7(8):1129-35. doi: 10.1517/14712598.7.8.1129.
Cancers are composed of heterogeneous cell populations, including highly proliferative immature precursors and differentiated cells, which may belong to different lineages. Recent advances in stem cell research have demonstrated the existence of tumour-initiating, cancer stem cells (CSCs) in non-solid and solid tumours. These cells are defined as CSCs because they show functional properties that resemble those of their normal counterpart to a significant extent. This concept applies to CSCs from brain tumours and, particularly, to glioblastoma stem-like cells, which self-renew under clonal conditions and differentiate into neuron- and glia-like cells, and into aberrant cells, with mixed neuronal/astroglia phenotypes. Notably, across serial transplantation into immunodeficient mice, glioblastoma stem-like cells are able to form secondary tumours which are a phenocopy of the human disease. A significant effort is underway to identify both CSC-specific markers and the molecular mechanism that underpin the tumorigenic potential of these cells, for this will have a critical impact on the understanding of the origin of malignant brain tumour and the discovery of new and more specific therapeutic approaches. Lately, the authors have shown that some of the bone morphogenetic proteins can reduce the tumorigenic ability of CSCs in GBMs. This suggests that mechanisms regulating the physiology of normal brain stem cells may be still in place in their cancerous siblings and that this may lead to the development of cures that selectively target the population CSCs found in the patients' tumour mass.
癌症由异质性细胞群体组成,包括高增殖性的未成熟前体细胞和分化细胞,这些细胞可能属于不同的谱系。干细胞研究的最新进展表明,在非实体瘤和实体瘤中存在肿瘤起始细胞,即癌症干细胞(CSCs)。这些细胞被定义为癌症干细胞,因为它们在很大程度上表现出与其正常对应细胞相似的功能特性。这一概念适用于来自脑肿瘤的癌症干细胞,尤其是胶质母细胞瘤干细胞样细胞,它们在克隆条件下自我更新,并分化为神经元样细胞、胶质样细胞以及具有混合神经元/星形胶质细胞表型的异常细胞。值得注意的是,通过连续移植到免疫缺陷小鼠体内,胶质母细胞瘤干细胞样细胞能够形成继发性肿瘤,这些继发性肿瘤是人类疾病的拟表型。目前正在做出巨大努力来鉴定癌症干细胞特异性标志物以及支撑这些细胞致瘤潜力的分子机制,因为这将对理解恶性脑肿瘤的起源以及发现新的、更具特异性的治疗方法产生关键影响。最近,作者们发现一些骨形态发生蛋白可以降低胶质母细胞瘤中癌症干细胞的致瘤能力。这表明调节正常脑干细胞生理学的机制在其癌变的同类细胞中可能仍然存在,并且这可能会促使开发出能够选择性靶向患者肿瘤块中癌症干细胞群体的治疗方法。