Generation of Breast Cancer Stem Cells by the EMT
Annual rept. 15 Sep 2008-14 Sep 2009
WHITEHEAD INST FOR BIOMEDICAL RESEARCH CAMBRIDGE MA
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The epithelial-mesenchymal transition EMT has been found by us to induce normal mammary epithelial cells MECs to acquire mesenchymal traits and, in addition, many of the characteristics of mammary epithelial stem cells. At the same time, induction of an EMT in breast cancer cells causes them to acquire to many of the attributes of cancer stem cells CSCs. However, none of these observations demonstrate that the products of EMT are actually stem cells. To demonstrate this, we developed a protocol for the efficient expression of EMT-inducing transcription factors in vector-infected cells. We have now demonstrated in initial experiments that induction of an EMT in normal mouse MECs results in a 100-fold increase in their ability to generate mammary ductal trees. Hence, an EMT can indeed increase the formation of normal mammary epithelial stem cells. Attempts to produce the parallel result with human breast cancer cells have not advanced as far. Since we can now produce large numbers of cells with properties of human breast cancer stem cells, we have used these to screen for drugs that preferentially kill human CSCs and have found two agents that preferentially eliminate CSCs.
- Medicine and Medical Research