Invasive basal cell carcinomas [BCCs] appear to only arise where a skin stem cell is the site of the original oncogenic mutation, while lesions that originate from progenitor cells remain benign, researchers suggest in a study published online in Nature (July 8, 2016).
In order to understand the changes in cell dynamics that follow an oncogenic mutation, which the authors note are currently unknown, investigators used a transgenic mouse model in which an oncogene had been coupled with a fluorescent marker. Cells where the oncogene had been activated, and their daughter cells, would then be easily tracked and counted.
Mathematical modelling on the data from the fluorescing cells showed that only daughter cells that had arisen from stem cells with the oncogenic mutation active were able to overcome apoptosis and multiply into a basal cell carcinoma. In contrast, the growth of daughter cells derived from progenitor cells becomes checked by increasing levels of apoptosis.
“It’s incredibly rare to identify a cancer cell of origin and until now no one has been able to track what happens on an individual level to these cells as they mutate and proliferate,” says Dr. Cedric Blanpain, senior author on the paper and principal investigator at the Cedric Blanpain Lab at Université Libre de Bruxelles in Brussels, Belgium, in a press release. “We now know that stem cells are the culprits: when an oncogene in a stem cell becomes active, it triggers a chain reaction of cell division and proliferation that overcomes the cell’s safety mechanisms.”
“While this has solved a long-standing scientific argument about which cell types can lead to invasive skin tumours, it is far more than just a piece of esoteric knowledge,” said study author Professor Ben Simons from the Cavendish Laboratory at the University of Cambridge, in Cambridge, U.K.
“It suggests to us that targeting the pathways used in regulating cell fate decisions—how stem cells choose between cell proliferation and differentiation—could be a more effective way of halting tumours in their tracks and lead to potential new therapies.”