Tang Carol, Chua Constance L M, Ang Beng-Ti
Department of Research, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433.
Ann Acad Med Singap. 2007 May;36(5):352-7.
Not all cancer cells are born equal. While the great majority of the cells that make up tumours are destined to differentiate, albeit aberrantly, and eventually stop dividing, a handful of cancer cells appear to possess limitless replicative potential. This review presents compelling evidence to suggest that the bulk of malignant cells of most cancers are generated by a rare fraction of stem cell-like cancer cells. These cells, dubbed cancer stem cells, are phenotypically similar to the normal stem cells of the corresponding tissue of origin, but they exhibit dysfunctional patterns of self-renewal and differentiation. Cancer stem cells that are capable of recapitulating brain tumours as xenografts in mice are characterised by defined stem cell markers. These brain tumour stem cells demonstrate enhanced chemoresistance and radioresistance mechanisms compared to non-stem cells in the heterogeneous tumour, which suggest that they may be the likely candidates for tumour progression and recurrence. Indeed, recent work has shown that such aberrant signalling pathways may be targeted in novel anti-cancer therapeutic strategies. The stem cell concept of tumour progression prompts immediate attention to a new paradigm in cancer research with a focus on this minority subset of cells, and the design of novel therapeutic strategies to target these cells that are insignificant within the population of tumour cells, but that are in fact the relevant cells to be destroyed.
并非所有癌细胞都是生来平等的。构成肿瘤的绝大多数细胞尽管会异常分化，但最终会停止分裂，然而仍有少数癌细胞似乎具有无限的复制潜能。这篇综述提供了令人信服的证据，表明大多数癌症的大部分恶性细胞是由一小部分干细胞样癌细胞产生的。这些细胞被称为癌症干细胞，在表型上与相应起源组织的正常干细胞相似，但它们表现出自我更新和分化的功能失调模式。能够在小鼠体内作为异种移植重现脑肿瘤的癌症干细胞具有特定的干细胞标志物。与异质性肿瘤中的非干细胞相比，这些脑肿瘤干细胞表现出更强的化学抗性和放射抗性机制，这表明它们可能是肿瘤进展和复发的潜在候选者。事实上，最近的研究表明，这种异常的信号通路可能是新型抗癌治疗策略的靶点。肿瘤进展的干细胞概念促使人们立即关注癌症研究中的一个新范式，即关注这一少数细胞亚群，并设计针对这些细胞的新型治疗策略，这些细胞在肿瘤细胞群体中所占比例微不足道，但实际上却是需要被消灭的相关细胞。
