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  • Review Article
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Contribution of stem cells and differentiated cells to epidermal tumours

Nature Reviews Cancer volume 3, pages 444–451 (2003)Cite this article

Key Points

  • Epidermal stem-cell progeny give rise to the differentiated cells of the interfollicular epidermis (IFE), hair follicles and sebaceous glands.

  • Multipotent epidermal stem cells are likely to be the main target cells for the various types of epidermal tumour.

  • Differentiated cells can regulate the clonal expansion of mutant stem-cell clones.

  • Epidermal cancer comprises many different tumour types, including basal-cell carcinoma (BCC), squamous-cell carcinoma (SCC), trichofolliculoma, pilomatricoma and sebaceous adenoma.

  • Factors responsible for the genesis of specific tumour types have been identified. Some, such as RAS and p53, are important for growth, and others, such as β-catenin, are important for determining differentiated characteristics.

Abstract

The outer covering of the skin — the epidermis — is subject to sustained environmental assaults. As a result, many cells acquire potentially oncogenic mutations. Most cells are lost through differentiation, and only long-term epidermal residents, such as stem cells, accumulate the number of genetic hits that are necessary for tumour development. So, what genetic and environmental factors determine whether a mutant stem cell forms a tumour and what type of tumour will develop?

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Figure 1: Diversity of epidermal tumours reflects the range of differentiated cell types in normal epidermis.
Figure 2: The epidermal stem-cell compartment gives rise to distinct cell lineages and tumour types.
Figure 3: Models of epidermal lineage and clonal expansion in human interfollicular epidermis.
Figure 4: Contributions of differentiated cells to epidermal cancer.
Figure 5: The Sonic Hedgehog pathway.
Figure 6: The WNT pathway.

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Acknowledgements

The authors are grateful to Cancer Research UK and a European Union Quality of Life Network grant for financial support. We thank C. Lo Celso, D. Prowse and C. Niemann for providing micrographs for figure 1 and S. Lyle for his advice.

Author information

Authors and Affiliations

  1. Cancer Research UK, London Research Institute, Keratinocyte Laboratory, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    David M. Owens & Fiona M. Watt

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  1. David M. Owens
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Correspondence to Fiona M. Watt.

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DATABASES

LocusLink

α-catenin

β-catenin

CYLD

Delta1

folliculin

Gli1

Hras

IL-1α

Indian Hedgehog

α3β1 integrin

α6β4 integrin

β1 integrin

Lef1

LEF1

Myc

Notch1

PTCH

Pten

RAS

SHH

SMO

TGF-β

TP53

Trp53

VEGF

Glossary

APOCRINE GLAND

A tubular gland of secretory cells that functions primarily to produce scent.

ECCRINE GLAND

A tubular gland of secretory cells that functions primarily in heat regulation through the production of sweat.

KERATINOCYTE

The most abundant cell type in the epidermis. Keratinocytes are epithelial cells and produce hair follicles, sweat and sebaceous glands, and the outer covering of the skin.

INTEGRINS

Heterodimeric transmembrane glycoproteins that are receptors for extracellular-matrix proteins.

DMBA

(7,12-Dimethylbenz[a]anthracene). Bay-region diol-epoxide-type chemical carcinogen. Induces an A→T transversion of codon 61 in Hras.

TUMOUR PROMOTER

Induces epigenetic changes that select for clonal expansion of mutated cells. The phorbol ester type, TPA, is the most widely used tumour promoter in mouse skin carcinogenesis models.

ADHERENS JUNCTION

A cell–cell adhesive junction that contains classical cadherins.

GAP JUNCTION

A cell–cell junction that mediates intercellular communication.

COWDEN DISEASE

Autosomal-dominant disease that features multiple trichilemmomas.

GORLIN'S SYNDROME

A hereditary predisposition to basal-cell carcinomas.

FAMILIAL CYLINDROMATOSIS

Autosomal dominantly inherited syndrome in which tumours have eccrine or apocrine glandular differentiation.

MUIR–TORRE SYNDROME

A condition that results in multiple sebaceous tumours and multiple visceral carcinomas.

MISMATCH REPAIR

A genomic system that detects and repairs incorrectly paired nucleotides that are introduced during DNA replication. Proteins involved include MSH2 and MLH1.

MICROSATELLITE INSTABILITY

Characterized by the accumulation of somatic alterations in the length of simple, repeated nucleotide sequences (called 'microsatellites').

BIRT–HOGG–DUBE SYNDROME

A condition that is characterized by hair-follicle and kidney tumours.

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Owens, D., Watt, F. Contribution of stem cells and differentiated cells to epidermal tumours. Nat Rev Cancer 3, 444–451 (2003). https://doi.org/10.1038/nrc1096

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