Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi.

Area of Science:

• Oncology
• Dermatology
• Stem Cell Biology

Background:

• Distinguishing malignant from benign tumors is crucial for treating life-threatening cancers.
• Acral melanomas, a deadly skin cancer, require understanding their origins and invasive potential.

Purpose of the Study:

• To investigate if human acral melanomas originate from distinct melanocyte stem cells.
• To explore the cellular dynamics underlying melanoma invasiveness using mouse models and human samples.

Main Methods:

• Developed fate-tracing technologies for melanocyte stem cells in sweat glands (glandular McSCs).
• Utilized mouse models of melanoma and analyzed human melanocytic lesions from volar skin.

Main Results:

• Glandular McSCs self-renew and generate migratory progeny, forming invasive melanomas in mice that mimic human acral melanomas.
• Genetically unstable McSCs were observed expanding in sweat glands and epidermis in human melanomas, but not in nevi.

Conclusions:

• Glandular McSCs are a potential origin for invasive acral melanomas.
• Tracking McSC expansion dynamics in sweat glands and epidermis provides a novel approach for early differential diagnosis of acral melanomas from nevi.