Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
PLoS One. 2012;7(4):e35338. doi: 10.1371/journal.pone.0035338. Epub 2012 Apr 13.
There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Recent molecular profiling has identified six major subtypes of breast cancer: basal-like, ErbB2-overexpressing, normal breast epithelial-like, luminal A and B, and claudin-low subtypes. To help understand the relationship among mammary stem/progenitor cells and breast cancer subtypes, we have recently derived distinct hTERT-immortalized human mammary stem/progenitor cell lines: a K5(+)/K19(-) type, and a K5(+)/K19(+) type. Under specific culture conditions, bipotent K5(+)/K19(-) stem/progenitor cells differentiated into stable clonal populations that were K5(-)/K19(-) and exhibit self-renewal and unipotent myoepithelial differentiation potential in contrast to the parental K5(+)/K19(-) cells which are bipotent. These K5(-)/K19(-) cells function as myoepithelial progenitor cells and constitutively express markers of an epithelial to mesenchymal transition (EMT) and show high invasive and migratory abilities. In addition, these cells express a microarray signature of claudin-low breast cancers. The EMT characteristics of an un-transformed unipotent mammary myoepithelial progenitor cells together with claudin-low signature suggests that the claudin-low breast cancer subtype may arise from myoepithelial lineage committed progenitors. Availability of immortal MPCs should allow a more definitive analysis of their potential to give rise to claudin-low breast cancer subtype and facilitate biological and molecular/biochemical studies of this disease.
越来越多的证据表明，乳腺癌和其他癌症起源于一小部分具有自我更新特性的干细胞/祖细胞，并由这些细胞维持。最近的分子分析已经确定了六种主要的乳腺癌亚型：基底样、ErbB2 过表达型、正常乳腺上皮样型、luminal A 和 B 型，以及 Claudin-low 亚型。为了帮助理解乳腺干细胞/祖细胞与乳腺癌亚型之间的关系，我们最近分离出了具有不同特征的 hTERT 永生化人乳腺干细胞/祖细胞系：一种 K5(+)/K19(-)型，和一种 K5(+)/K19(+)型。在特定的培养条件下，双潜能 K5(+)/K19(-)干细胞/祖细胞分化为稳定的克隆群体，这些克隆群体是 K5(-)/K19(-)，具有自我更新和单潜能肌上皮分化潜能，而与亲本 K5(+)/K19(-)细胞不同，后者是双潜能的。这些 K5(-)/K19(-)细胞作为肌上皮祖细胞发挥作用，并且持续表达上皮到间充质转化（EMT）的标志物，并表现出高侵袭性和迁移能力。此外，这些细胞表达 Claudin-low 乳腺癌的微阵列特征。未转化的单潜能乳腺肌上皮祖细胞的 EMT 特征以及 Claudin-low 特征提示 Claudin-low 乳腺癌亚型可能起源于肌上皮谱系定向祖细胞。永生 MPC 的可用性应该允许更明确地分析它们产生 Claudin-low 乳腺癌亚型的潜力，并促进对这种疾病的生物学和分子/生化研究。
