Mani 2008: the epithelial-mesenchymal transition generates cells with properties of stem cells
Switching on the invasion programme in normal breast cells also gave them stem cell properties, linking two ideas about how cancers spread and resist treatment, and suggesting that the mobile cells that seed metastases are the same ones that can regrow a tumour.
Overview
Mani, Weinberg and colleagues induced an epithelial-mesenchymal transition in immortalised human mammary epithelial cells by expressing the transcription factors Snail or Twist or by exposing them to TGF-beta1. The cells acquired a mesenchymal appearance, a CD44-high CD24-low surface profile matching that of breast cancer stem cells, and a much greater ability to form mammospheres and colonies. Conversely, stem-like cells isolated from normal and cancerous breast tissue expressed EMT markers. The paper connected the EMT and cancer stem cell fields.
- Inducing EMT in human mammary epithelial cells produced CD44-high CD24-low cells with increased mammosphere and colony formation.
- Stem-like cells from normal and malignant breast tissue expressed EMT markers.
- EMT-inducing factors also increased the tumour-initiating ability of transformed cells.
This paper is why metastasis, stemness and therapy resistance are now studied as one problem. It suggests that the cells most able to spread are also the ones most able to regrow, and it motivates therapies that target the mesenchymal or stem-like state.
- Cell culture and mouse work with engineered cells; relevance to spontaneous human tumours is inferred.
- Later work suggests partial EMT states, rather than complete transitions, carry the most stemness and metastatic ability.
Similar pages
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