Daily Archives: August 12, 2019

How To Turn Breast Cancer Cells Into Fat to Stop Them From Spreading

Researchers have been able to coax human breast cancer cells to turn into fat cells in a new proof-of-concept study in mice. To achieve this feat, the team exploited a weird pathway that metastasising cancer cells have; their results are just a first step, but it’s a truly promising approach. When you cut your finger, or when a foetus grows organs, the epithelium cells begin to look less like themselves, and more ‘fluid’ – changing into a type of stem cell called a mesenchyme and then reforming into whatever cells the body needs.

This process is called epithelial-mesenchymal transition (EMT) and it’s been known for a while that cancer can use both this one and the opposite pathway called MET (mesenchymal‐to‐epithelial transition), to spread throughout the body and metastasise. The researchers took mice implanted with an aggressive form of human breast cancer, and treated them with both a diabetic drug called rosiglitazone and a cancer treatment called trametinib. Thanks to these drugs, when cancer cells used one of the above-mentioned transition pathways, instead of spreading they changed from cancer into fat cells – a process called adipogenesis.

The image  shows this process, with the cancer cells tagged with a green fluorescent protein and normal red fat cell on the left. The cancer-turned-fat cells display as brown (on the right) because the red of the fat cells combines with the green of the protein cancer cell tag.

The models used in this study have allowed the evaluation of disseminating cancer cell adipogenesis in the immediate tumour surroundings,” the team wrote in their paper, published in January 2019. “The results indicate that in a patient-relevant setting combined therapy with rosiglitazone and trametinib specifically targets cancer cells with increased plasticity and induces their adipogenesis.

Although not every cancer cell changed into a fat cell, the ones that underwent adipogenesis didn’t change back. “The breast cancer cells that underwent an EMT not only differentiated into fat cells, but also completely stopped proliferating,” said senior author Gerhard Christofori, a biochemist at the University of Basel, in Switzerland. “As far as we can tell from long-term culture experiments, the cancer cells-turned-fat cells remain fat cells and do not revert back to breast cancer cells.

So how does this work? Well, as a drug trametinib both increases the transition process of cells – such as cancer cells turning into stem cells – and then increases the conversion of those stem cells into fat cellsRosiglitazone was less important, but in combination with trametinib, it also helped the stem cells convert into fat cells. “Adipogenic differentiation therapy with a combination of rosiglitazone and [trametinib] efficiently inhibits cancer cell invasion, dissemination, and metastasis formation in various preclinical mouse models of breast cancer,” wrote the team.

Source: https://www.cell.com/
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https://www.sciencealert.com/