School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, UK.
School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, UK ; Center for Genetics and Genomics and Cancer Research Nottingham, University of Nottingham, University Park, Nottingham, UK.
Breast Cancer (Dove Med Press). 2012 Oct 26;4:155-66. doi: 10.2147/BCTT.S26434.
The discovery that breast cancers contain stem-like cells has fuelled exciting research in the last few years. These cells are referred to as breast cancer stem cells (BCSCs) and are thought to be involved in tumor initiation, progression, and metastasis. Being intrinsically resistant to chemo- and radiotherapy, they are also considered responsible for recurrence of the disease after treatment. BCSCs have been suggested to be at the basis of tumor complexity, as they have the ability to self-renew and give rise to highly proliferating and terminally differentiated cancer cells that comprise the heterogeneous bulk of the tumor. There has been much speculation on the BCSC model, and in this review we address some fundamental questions, such as the identity of BCSCs and their involvement in tumor intra- and interheterogeneity. As an alternative to the BCSC model, we discuss clonal evolution, as both theories show extensive evidence in support of their arguments. Finally, we discuss a unifying idea that reconciles both models, which is based on stem cell plasticity and epigenetic modifications induced by the tumor microenvironment. The implications of cancer stem cell plasticity for drug discovery and future therapeutic interventions are presented.
近年来，人们发现乳腺癌中存在类干细胞，这一发现激发了令人兴奋的研究。这些细胞被称为乳腺癌干细胞（BCSCs），被认为与肿瘤的起始、进展和转移有关。由于它们对化疗和放疗具有内在的抗性，因此也被认为是治疗后疾病复发的原因。BCSCs 被认为是肿瘤复杂性的基础，因为它们具有自我更新的能力，并产生高度增殖和终末分化的癌细胞，这些细胞构成了肿瘤异质性的大部分。人们对 BCSC 模型进行了大量推测，在这篇综述中，我们探讨了一些基本问题，例如 BCSC 的身份及其在肿瘤内异质性和间质异质性中的作用。作为 BCSC 模型的替代方案，我们讨论了克隆进化，因为这两种理论都有大量证据支持其论点。最后，我们讨论了一个统一的观点，即基于肿瘤微环境诱导的干细胞可塑性和表观遗传修饰，该观点调和了这两种模型。本文还介绍了癌症干细胞可塑性对药物发现和未来治疗干预的意义。
