Breast cancer cells coaxed into turning into fat cells.
It is known that epithelial-mesenchymal transition (EMT) is a process by which a polarized epithelial cell to assume a mesenchymal cell phenotype, which includes enhanced migratory capacity, invasiveness, and elevated resistance to apoptosis; understandably EMT is also utilised by tumours to metastasize. Now, researchers from the University of Basel have harnessed EMT to coax breast cancer cells in mice to turn into harmless fat cells. The team state that the breast cancer cells also stopped proliferating and prevented metastasis of the main tumour site. The opensource study is published in the journal Cancer Cell.
Previous studies show that EMT is essential for embryonic development, during which 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 and 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. EMT is implicated in cancer’s ability to metastasize and plasticise. The current study investigates whether EMT-derived cancer cell plasticity necessary for cancer spread can be directly targeted and inhibited by differentiation into fat cells.
The current study utlilises the combination of two drugs, namely, Rosiglitazone, which is widely used to treat patients with diabetes, and Trametinib, which inhibits the growth and spread of cancer cells. Results show this combination of the two active substances converts breast cancer cells, which divide quickly and form metastases, into fat cells which can no longer divide or metastasize.
The group explain that they targeted a handful of aggressive cancer cells which had left the primary tumour and invaded the surrounding tissue. They go on to add these cells, which most likely had undergone an EMT, were readily converted to fat cells, while the remaining cancer cells within the tumour were no longer able to proliferate to invade the neighbouring tissue and blood vessels, or metastasize.
The team surmise 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 that that 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 EMT-targeted differentiation approach in combination with existing chemotherapies and other types of cancers.
Source: University Basel