Mani Sendurai A, Guo Wenjun, Liao Mai-Jing, Eaton Elinor Ng, Ayyanan Ayyakkannu, Zhou Alicia Y, Brooks Mary, Reinhard Ferenc, Zhang Cheng Cheng, Shipitsin Michail, Campbell Lauren L, Polyak Kornelia, Brisken Cathrin, Yang Jing, Weinberg Robert A
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Cell. 2008 May 16;133(4):704-15. doi: 10.1016/j.cell.2008.03.027.
The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.
上皮-间质转化(EMT)是一个关键的发育程序,在癌症侵袭和转移过程中常常被激活。我们在此报告,永生化人乳腺上皮细胞(HMLEs)中EMT的诱导导致间充质特征的获得以及干细胞标志物的表达。此外,我们表明这些细胞形成乳腺球的能力增强,这是一种与乳腺上皮干细胞相关的特性。与此无关的是,从HMLE培养物中分离出的干细胞样细胞形成乳腺球并表达与经历EMT的HMLEs相似的标志物。此外,从小鼠或人乳腺或乳腺癌中分离出的干细胞样细胞表达EMT标志物。最后,经历EMT的转化人乳腺上皮细胞更有效地形成乳腺球、软琼脂集落和肿瘤。这些发现说明了EMT与上皮干细胞特性获得之间的直接联系。