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Review
. 2016 Sep;10(3):191-196.
doi: 10.1007/s12079-016-0349-3. Epub 2016 Aug 23.

Crosstalk in skin: melanocytes, keratinocytes, stem cells, and melanoma

Joshua X Wang  1 , Mizuho Fukunaga-Kalabis  1 , Meenhard Herlyn  2
Affiliations
Review

Crosstalk in skin: melanocytes, keratinocytes, stem cells, and melanoma

Joshua X Wang et al. J Cell Commun Signal. 2016 Sep.

Abstract

In the vertebrate embryo, melanocytes arise from the neural crest, migrate to and colonize the basal layer within the skin and skin appendages. Post-migratory melanocytes are securely attached to the basement membrane, and their morphology, growth, adhesion, and migration are under control of neighboring keratinocytes. Melanoma is a malignant tumor originated from melanocytes or their progenitor cells. During melanocyte transformation and melanoma progression, melanocytes lose their interactions with keratinocytes, resulting in uncontrolled proliferation and invasion of the malignant cells. Melanoma cells at the advanced stages often lack melanocytic features and resemble multipotent progenitors, which are a potential melanocyte reservoir in human skin. In this mini-review, we will summarize findings on cell-cell interactions that are responsible for normal melanocyte homeostasis, stem cell self-renewal, and differentiation. Our ultimate goal is to define molecules and pathways, which are essential for normal cell-cell interactions but deregulated in melanoma formation and progression.

Keywords: Cell-cell interaction; Keratiocyte; Melanocyte; Melanoma; Stem cell.

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Figures

Fig. 1
Fig. 1
Within the epidermis, melanocytes adhere to the basement membrane primarily through α6β1 integrin contacts with laminin. UV radiation causes skin keratinocytes to release pro-inflammatory cytokine IL-1β, which is taken up by melanocytes. In response, melanocytes release CCN3, and in an autocrine manner, up-regulates receptor tyrosine kinase DDR1. This increases adherence with the basement membrane through contact with collagen IV
Fig. 2
Fig. 2
Neural crest stem cell (NCSC)-like cells reside in a dermal niche with high Notch and low NUMB activity and contain self-renewal capability. Upon UV irradiation in 3D skin reconstructs, keratinocytes release Wnt ligands that control melanocyte homeostasis. The ligands bind to receptors on NCSC-like cells, inhibit selfrenewal, and induce differentiation into melanocytes
See this image and copyright information in PMC

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