Breast-cancer stem cells-beyond semantics
Breast-cancer stem cells-beyond semantics
复制标题
DOI：
10.1016/s1470-2045(11)70191-7
复制
发表时间：
2012-01-01
期刊：
影响因子：
51.1
通讯作者：
Nakshatri, Harikrishna
中科院分区：
文献类型：
--
作者：
Badve, Sunil;Nakshatri, Harikrishna
乳腺癌的瘤内异质性已有充分记载。尽管导致这种异质性的机制尚不清楚，但有一种癌细胞亚群，即癌症干细胞（CSCs），其与成体组织干细胞具有某些表型相似性，被认为是导致肿瘤异质性的原因之一。据推测，这些癌症干细胞处于休眠状态，由于其增殖活性低以及能够排除细胞内毒素，它们对化疗和放疗具有抗性。这些细胞最初是基于CD44、CD24和ALDH1等标志物的存在而被分离出来的，通过乳腺球形成实验以及移植到免疫缺陷小鼠体内进行了进一步的特性鉴定。癌症干细胞假说引发了几个理论和实践问题。癌症是在正常乳腺干细胞中产生的，还是一些恶性细胞通过克隆进化获得了癌症干细胞表型？不同分子（内在）亚型的乳腺癌中的癌症干细胞是否相似，或者它们基于亚型是否具有不同的特性？癌症干细胞表型是否反映了少数癌细胞的可塑性或动态特性？当这些细胞经历上皮 - 间质转化，并在转移部位根据肿瘤微环境和转移部位特异性的信号线索恢复到上皮表型时，它们是如何获得侵袭行为的？人们越来越认识到，用于识别癌症干细胞的方法和检测手段存在很大的局限性；这是否会否定整个概念呢？在本文的个人观点中，我们认为癌症干细胞表型代表了一个具有侵袭性的克隆，它通过癌症的各种特征的不断进化和整合在恶劣环境中生存。这种进化可能涉及获得允许不对称和对称分裂的突变，将宿主的免疫攻击转化为自身优势，以及通过黏附分子的可逆变化适应转移部位的可塑性。我们还认为，癌症的细胞类型起源可能会影响癌症干细胞在肿瘤中发展的速度，最终影响疾病的预后。
Intratumoral heterogeneity in breast cancer is well documented. Although the mechanisms leading to this heterogeneity are not understood, a subpopulation of cancer cells, cancer stem cells (CSCs), that have some phenotypic similarities with adult tissue stem cells, has been suggested to contribute to tumour heterogeneity. It has been postulated that these CSCs are dormant, and by virtue of their low proliferative activity and ability to exclude intracellular toxins, are resistant to chemotherapy and radiation therapy. These cells were initially isolated based on the presence of markers such as CD44, CD24, and ALDH1, with further characterisation using mammosphere assay and transplantation into immunodeficient mice. The CSC hypothesis raises several theoretical and practical questions. Does cancer arise in normal mammary stem cells or do some malignant cells acquire a CSC phenotype through clonal evolution? Are CSCs in different molecular (intrinsic) subtypes of breast cancer similar, or do they have distinct properties based on the subtype? Does the CSC phenotype reflect plasticity or the dynamic nature of a few cancer cells? How do these cells acquire invasive behaviour, as they go through epithelial-to-mesenchymal transition and then revert to epithelial phenotype at sites of metastasis in response to tumour microenvironmental and metastasis site-specific cues? It is increasingly recognised that the methods and assays used for identifying CSCs have substantial limitations; does this negate the entire concept? In this Personal View, we argue that the CSC phenotype represents an aggressive clone that survives in an adverse environment through constant evolution and integration of various hallmarks of cancer. This evolution could involve acquiring mutations that permit asymmetric and symmetric division, converting the host immune attack to its own advantage, and plasticity to adapt to sites of metastasis through reversible change in adhesion molecules. We also argue that the cell-type origin of cancer could affect the rate at which CSCs develop in a tumour, with an eventual effect on disease outcome.