Cancer cells can adapt to changing conditions using a cellular process that usually takes place during embryonic development. When the cells receive certain external signals, they pass through the so-called epithelial-mesenchymal transition (EMT). In this process, epithelial cells are transformed into a stem-cell-like state.
EMT is important for the development of organs in embryos: The cells become mobile and can differentiate into different cell types. In adults, this cellular remodeling program is usually only used for wound healing. However, EMT can also be activated in cancer cells and enables them to form metastases. Since the cancer cells are particularly adaptable in this phase, this might offer a starting point for potential therapies.
Dana Ishay Ronen, University of Basel, Switzerland, and colleagues have used mice with particularly aggressive human breast cancer tumors to see whether EMT can be used to reprogram the cancer cells into more harmless variants. Over a period of three weeks, the mice were given the anti-cancer drug trametinib and rosiglitazone, which is used in diabetes treatment. Earlier studies had shown that rosiglitazone can stimulate malignant cells to re-differentiate.
The researchers found that breast cancer cells that underwent EMT developed into fat cells that could hardly be distinguished from normal fat cells. While cancer spread into the lungs of the control animals, the animals treated with the combination therapy did not develop metastases. Further cell experiments indicated that once converted, the former cancer cells remain fat cells. Although the therapy is unable to completely transform the primary tumor into fat, the reprogramming of a critical number of tumor cells could make the tumor more sensitive to conventional chemotherapy.
- Gain Fat—Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis,
Dana Ishay-Ronen, Maren Diepenbruck, Ravi Kiran Reddy Kalathur, Nami Sugiyama, Stefanie Tiede, Robert Ivanek, Glenn Bantug, Marco Francesco Morini, Junrong Wang, Christoph Hess, Gerhard Christofori,
Cancer Cell 2019, 35, 17–32.e6.