Some of the most deadly skin cancers may start in stem cells that lend colour to hair, and originate in hair follicles rather than in skin layers, says a new study.
Hair follicles are complex organs that reside within skin layers. It is there that immature pigment-making cells develop cancer-causing genetic changes - and in a second step - are exposed to normal hair growth signals.
The study, published in the journal Nature Communications, found that unlike their normal counterparts, newly cancerous pigment stem cells then migrate up and out of the follicles to establish melanomas in nearby surface skin before spreading deeper.
The study was conducted in genetically engineered mice, with the results confirmed in human tissue samples.
"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," said study author Mayumi Ito Suzuki, Associate Professor at New York University.
The study addresses the stem cells that mature into melanocytes, cells that make the protein pigment melanin, which protects skin by absorbing some of the sun's ultraviolet, DNA-damaging rays.
By absorbing some wavelengths of visible light, but reflecting others, pigments "create" hair colour.
In a series of elegant steps, the research team established a new mouse model for the study of melanoma, one engineered such that the team could edit genes in follicular melanocyte stem cells only (the c-Kit-CreER mouse).
This capability enabled researchers to introduce genetic changes that made only melanoctye stem cells - and their descendants destined to form melanomas - glow no matter where they travelled.
Able to accurately track a key stem cell type for the first time, the authors confirmed that melanoma cells can arise from melanocyte stem cells, which abnormally migrate up and out of hair follicles to enter the epidermis, the outermost layer of skin.
The team then tracked the same cells as they multiplied there, and then moved deeper into the skin layer called the dermis.
Once there, the cells shed the markers and pigment that went with their follicular origins, presumably in response to local signals.
They also acquired signatures similar to nerve cells (neurons) and skin cells (mesenchymal), molecular characteristics "almost exactly like" those noted in examinations of human melanoma tissue.
Knowing where to look for the original, cancer-causing event, the researchers temporarily eliminated signals one by one in the follicular environment to see if cancer still formed in their absences.
"Our mouse model is the first to demonstrate that follicular oncogenic melanocyte stem cells can establish melanomas, which promises to make it useful in identifying new diagnostics and treatments for melanoma," said first study author Qi Sun.