In cancer, epithelial-mesenchymal transition (EMT) is a process where tumors assume a mesenchymal cell phenotype to enhance metastasis, invasiveness, and elevated resistance to cell death. Now, researchers from the University of Basel harness EMT to coax breast cancer cells in mice to turn into harmless fat cells. The team states the breast cancer cells also stopped proliferating and prevented metastasis of the main tumor site. The opensource study is published in the journal Cancer Cell.
Previous studies show EMT is essential for embryonic development where stem cells differentiate into a variety of cell types throughout the body, and for tissue regeneration such as wound healing. As a result, resident cells can adopt the properties of other cell types to break away from their cell cluster. Once mobile, the cells migrate via the bloodstream to other regions of the body where they undergo a further conversion before taking root and forming new tissue structures. Therefore, EMT is implicated in cancer’s ability to metastasize and plasticize. The current study investigates whether EMT-derived cancer cell plasticity necessary for metastasis can be directly targeted and inhibited by being forced to differentiate into fat cells.
The current study utilizes the combination of two drugs, namely, Rosiglitazone, widely used to treat patients with diabetes, and Trametinib used to inhibit the growth and spread of cancer cells. Results show this combination of the two active substances converts breast cancer cells into fat cells rendered incapable of dividing or metastasizing.
The group explains they targeted a cluster of aggressive cancer cells that had left the primary tumor and invaded the surrounding tissue. They go on to add these cells had most likely undergone EMT so they were readily converted to fat cells. They go on to add the remaining cancer cells within the tumor were no longer able to proliferate to invade the neighboring tissue and blood vessels or metastasize.
The team surmises they have successfully forced the differentiation of EMT-derived breast cancer cells into functional and stable fat cells in mice. For the future, the researchers state forcing a critical mass of cancerous cells to differentiate into fat cells could deplete a tumor’s ability to fight off conventional chemotherapy, and plan to test the EMT-targeted differentiation approach in combination with existing chemotherapies and other types of cancers.
Source: University Basel
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