Researchers have modeled the mechanism behind pigment-giving stem cells that give rise to skin cancers.
Researchers have demonstrated that mutations arising in melanocyte stem cells (McSCs), which originate in hair follicles, may be responsible for some melanomas. McSCs differentiate into a variety of cells including pigment cells, responsible for hair color.
The study, published in Nature Communications, demonstrated that oncogenic McSCs migrate out of hair follicles, spreading deeper into surrounding skin cells. Previous studies have been unable to draw accurate conclusions regarding the role of McSCs using murine models, due to key differences in the mechanisms involved in human melanoma compared with mouse melanoma.
“By confirming that oncogenic pigment cells in hair follicles are a bona fide source of melanoma, we have a better understanding of this cancer’s biology and new ideas about how to counter it,” commented study leader Mayumi Ito Suzuki (NYU Langone, NY, USA).
A transgenic mouse model was utilized, having been developed to mimic key features of human melanoma. GFP tags were inserted downstream of key McSC genes, giving the researchers the ability to track expression and later migration.
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Unexpectedly, aberrantly mutated McSCs were imaged migrating from hair follicles to the epidermis, before multiplying and moving deeper into the dermis. Once situated in the dermis, the McSCs lost their original pigment and markers, whilst developing signatures comparable to those found in human melanoma cells.
The team then eliminated individual signals within hair follicles to determine whether their loss halted the development of cancer. These findings demonstrated that, even if oncogenic mutations were present in McSCs, the process of multiplication and migration would not occur unless exposed to the signaling proteins endothelin or WNT.
These findings provide insight into a previously poorly understood cause of melanoma. Validation is needed, but once confirmed could form the basis of further research into prevention and treatment of melanoma.
“While our findings will require confirmation in further human testing, they argue that melanoma can arise in pigment stem cells originating both in follicles and in skin layers, such that some melanomas have multiple stem cells of origin,” concluded study author Qi Sun (NYU Langone).