School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, M20 4BX, UK.
Horm Cancer. 2011 Apr;2(2):91-103. doi: 10.1007/s12672-011-0066-6.
Developmentally, tumours can be viewed as aberrant versions of normal tissues. For example, tumours often retain differentiation markers of their tissue of origin. In addition, there is evidence that they contain cancer stem-like cells (CSCs) that drive tumourigenesis. In this review, we summarise current evidence that breast CSCs may partially explain endocrine resistance in breast cancer. In normal breast, the stem cells are known to possess a basal phenotype and to be mainly oestrogen receptor-α-negative (ER-). If the hierarchy in breast cancer reflects this, the breast CSC may be endocrine resistant because it expresses very little ER and can only respond to treatment by virtue of paracrine signalling from neighbouring, differentiated ER+ tumour cells. Normal breast epithelial stem cells are regulated by the epidermal growth factor receptor and other growth factor receptor signals. The observed increase in growth factor receptor expression in endocrine-resistant breast cancers may reflect a bigger proportion of CSCs selected by endocrine therapies. There is evidence from a number of studies that breast CSCs are ER- and EGR+/HER2+, which would support this view. It is reported that CSCs express mesenchymal genes, which are suppressed by ER expression, further indicating the mutual exclusion between ER+ cells and the CSCs. As we learn more about CSCs, differentiation and the expression and functional activity of the ER in these cells in diverse breast tumour sub-types, it is hoped that our understanding will lead to new modalities to overcome the problem of endocrine resistance in the clinic.
从发育的角度来看，肿瘤可以被视为正常组织的异常版本。例如，肿瘤通常保留其起源组织的分化标志物。此外，有证据表明它们含有驱动肿瘤发生的癌症干细胞（CSC）。在这篇综述中，我们总结了目前的证据，表明乳腺 CSC 可能部分解释了乳腺癌的内分泌抵抗。在正常乳腺中，已知干细胞具有基底表型，并且主要是雌激素受体-α阴性（ER-）。如果乳腺癌中的层次结构反映了这一点，那么乳腺 CSC 可能对内分泌治疗有抵抗性，因为它表达的 ER 非常少，只能通过来自邻近分化的 ER+肿瘤细胞的旁分泌信号来响应治疗。正常乳腺上皮干细胞受表皮生长因子受体和其他生长因子受体信号的调节。在内分泌抵抗性乳腺癌中观察到的生长因子受体表达增加可能反映了内分泌治疗选择的 CSC 比例更大。有多项研究的证据表明，乳腺 CSC 是 ER-和 EGR+/HER2+，这将支持这种观点。据报道，CSC 表达间充质基因，这些基因受 ER 表达抑制，进一步表明 ER+细胞和 CSC 之间的相互排斥。随着我们对 CSC、分化以及这些细胞中 ER 的表达和功能活性在不同乳腺肿瘤亚型中的了解不断增加，希望我们的理解将导致新的方法来克服临床中内分泌抵抗的问题。
