Melanoma can occur in hair follicles

Researchers from New York University School of Medicine and Perlmutter Cancer Center have found that the deadliest skin cancers may start in the stem cells that give hair color and originate in hair follicles.

The study, published online ahead of publication in Nature Communications (November 4, 2019), found that unlike their normal counterparts, newly cancerous pigment stem cells migrate upward from follicles, creating melanomas in the nearby surface of the skin and then spreading deeper. The study was conducted on genetically engineered mice, with results confirmed in human tissue samples.

“By confirming that tumorigenic pigment cells in hair follicles are the true source of melanoma, we better understand the biology of this cancer and new ideas about how to counter it,” said study author Dr. Mayumi Ito Suzuki, in a press release . Dr. Suzuki is is an assistant professor in the Ronald O. Perelman Department of Dermatology at New York University School of Medicine and Perlmutter Cancer Center.

Previous models of the disease suggested that sunlight was a major risk factor for melanoma, but current research suggests that the triggers are always present in normal follicles.

New research focuses on stem cells that develop into melanocytes. Cells that produce the pigment melanin, which protects the skin by absorbing some of the sun's DNA-damaging ultraviolet rays. By absorbing some waves of visible light but reflecting others, pigments “create” hair color.

In a series of steps, the NYU research team created a new mouse model to study melanoma. It is designed so that the team can only change genes in follicular melanocyte stem cells (c-Kit-CreER mouse). This ability allowed the researchers to introduce genetic changes that made only melanocyte stem cells, and their descendants destined to form melanomas glow no matter where they traveled.

By being able to precisely track key stem cell types for the first time, the study authors confirmed that melanoma cells may arise from melanocyte stem cells that migrate abnormally up and out of hair follicles, entering the epidermis. The team then tracked those same cells as they multiplied there and then drilled down into the skin layer.

Once in the dermis, the cells lose markers and pigment that came from their follicular origin, presumably in response to local signals. They also acquired signatures similar to nerve cells (neurons) and skin cells (mesenchymal), molecular characteristics similar to those noted in studies of human melanoma tissue.

Knowing where to look for the original cancer-causing event, the researchers temporarily eliminated the signals one by one in the follicular environment to see if cancer formed in their absence.

As a result, the researchers confirmed that follicular melanocyte stem cells, even though they had cancer-causing genetic mutations, did not proliferate or migrate to cause melanomas unless they were also exposed to endothelin (EDN) and WNT. These signaling proteins typically cause hairs to grow longer and pigment cells to multiply in the follicles.

“Our mouse model demonstrates for the first time that follicular oncogenic melanocyte stem cells can generate melanomas, which promises to make it useful for identifying new methods for diagnosing and treating melanoma,” said Dr. Qi Sun, a member of the research team.

Along with Ito Suzuki and Sun, study authors from the departments of dermatology, cell biology and pathology at New York University School of Medicine included Wendy Lee, Makoto Takeo, Chae Ho Lim, Markus Schober, Iman Osman and Rana Mubarak.

Source: http://www.derm.city/single-post/Some-skin-cancers-may-start-in-hair-follicles