Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi

Sally Eshiba; Takeshi Namiki; Yasuaki Mohri; Tomomi Aida; Naotaka Serizawa; Takakazu Shibata; Hironobu Morinaga; Daisuke Nanba; Yuichi Hiraoka; Kohichi Tanaka; Keiko Miura; Masaru Tanaka; Hisashi Uhara; Hiroo Yokozeki; Toshiaki Saida; Emi K Nishimura

doi:10.1016/j.celrep.2021.109492

Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi

Cell Rep. 2021 Aug 3;36(5):109492. doi: 10.1016/j.celrep.2021.109492.

Authors

Affiliations

¹ Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Dermatology, Tokyo Medical and Dental University Graduate School and Faculty of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
² Department of Dermatology, Tokyo Medical and Dental University Graduate School and Faculty of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: tnamderm@tmd.ac.jp.
³ Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
⁴ Department of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Laboratory of Genome Editing for Biomedical Research, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
⁵ Medical Corporation Shibata Dermatology Clinic, 1-1-30 Morinomiya Chuo, Chuo-ku, Osaka 540-0003, Japan.
⁶ Department of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
⁷ Department of Pathology, Tokyo Medical and Dental University Graduate School and Faculty of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
⁸ Department of Dermatology, Tokyo Women's Medical University Medical Center East, Tokyo, 2-1-10, Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan.
⁹ Department of Dermatology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
¹⁰ Department of Dermatology, Tokyo Medical and Dental University Graduate School and Faculty of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
¹¹ Shinshu University, 7-7-40-220 Kamiochiai, Chuo-ku, Saitama 338-0001, Japan.
¹² Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Division of Aging and Regeneration, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Electronic address: emikn@g.ecc.u-tokyo.ac.jp.

PMID: 34348144
DOI: 10.1016/j.celrep.2021.109492

Abstract

Early differential diagnosis between malignant and benign tumors and their underlying intrinsic differences are the most critical issues for life-threatening cancers. To study whether human acral melanomas, deadly cancers that occur on non-hair-bearing skin, have distinct origins that underlie their invasive capability, we develop fate-tracing technologies of melanocyte stem cells in sweat glands (glandular McSCs) and in melanoma models in mice and compare the cellular dynamics with human melanoma. Herein, we report that glandular McSCs self-renew to expand their migratory progeny in response to genotoxic stress and trauma to generate invasive melanomas in mice that mimic human acral melanomas. The analysis of melanocytic lesions in human volar skin reveals that genetically unstable McSCs expand in sweat glands and in the surrounding epidermis in melanomas but not in nevi. The detection of such cell spreading dynamics provides an innovative method for an early differential diagnosis of acral melanomas from nevi.

Keywords: acral melanomas; acral nevi; differential diagnosis; eccrine gland; melanocyte stem cell; melanoma model; pigment; risk factor; stem cells; sweat gland.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement* / radiation effects
Cell Proliferation / radiation effects
Cyclin D1 / metabolism
Disease Models, Animal
Epidermis / pathology
Epidermis / radiation effects
Gene Amplification
Genomic Instability / radiation effects
Melanocytes / pathology
Melanocytes / radiation effects
Melanoma / diagnosis
Melanoma / pathology*
Mice
Mice, Inbred C57BL
Nevus / pathology*
Risk Factors
Skin / pathology
Skin / radiation effects
Skin Pigmentation / radiation effects
Stem Cells / pathology*
Sweat Glands / radiation effects
Ultraviolet Rays

Substances

Cyclin D1