Stem Cells in Nonmelanoma Skin Cancer

January 2004

Wendy C. Weinberg, Stuart H. Yuspa

TLDR Stem cells play a key role in nonmelanoma skin cancers, with different origins and genetic changes linked to basal and squamous cell carcinomas.

The document discussed the role of stem cells in nonmelanoma skin cancers, specifically squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). It highlighted that SCC and BCC are clonal, while focal hyperplasias are polyclonal. Stem cells in the skin, particularly those in the hair follicle bulge, were identified as multipotent, capable of differentiating into various epidermal cells. BCCs were linked to follicular bulge stem cells and genetic changes in the Sonic Hedgehog pathway, while SCCs could originate from stem cells in different skin compartments, including the interfollicular epidermal proliferative unit (EPU). The study also noted that genetic or epigenetic changes in stem cell markers, such as integrins and telomerase, were associated with squamous cell neoplasms.

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Research cited in this study

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research Deregulated expression of c-Myc depletes epidermal stem cells

315 citations , June 2001 in “Nature Genetics”

research C-Myc Activation in Transgenic Mouse Epidermis Results in Mobilization of Stem Cells and Differentiation of Their Progeny

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c-Myc activation in mouse skin increases sebaceous gland growth and affects hair follicle development.

research Morphogenesis and Renewal of Hair Follicles from Adult Multipotent Stem Cells

949 citations , January 2001 in “Cell”

Adult mouse skin contains stem cells that can create new hair, skin, and oil glands.

research Involvement of Follicular Stem Cells in Forming Not Only the Follicle but Also the Epidermis

1010 citations , August 2000 in “Cell”

Hair follicle stem cells can form both hair follicles and skin.

research The Role of the Hairless (hr) Gene in the. Regulation of Hair Follicle Catagen Transformation

166 citations , July 1999 in “American Journal Of Pathology”

research Reversible Activation of c-Myc in Skin

467 citations , May 1999 in “Molecular Cell”

Activating c-Myc in skin causes rapid cell growth and changes, but these effects are reversible.

research Onset of Keratin 17 Expression Coincides with the Definition of Major Epithelial Lineages during Skin Development

318 citations , October 1998 in “The Journal of Cell Biology”

The study investigated the expression of keratin 17 (K17) during mouse skin development, revealing that K17 synthesis began in embryonic day 10.5 in a subset of epithelial cells. These cells later formed placodes, precursors to ectoderm-derived appendages like hair, glands, and teeth. The spatial distribution of K17 corresponded with lymphoid-enhancer factor (lef-1), a protein involved in epithelial–mesenchymal interactions. Ectopic expression of lef-1 in adult transgenic mice induced K17, suggesting a link between K17 expression, skin morphogenesis, and wound repair. This research highlighted the role of K17 in skin development and its potential involvement in epithelial lineage definition.

research The Malignant Capacity of Skin Tumors Induced by Expression of a Mutant H-Ras Transgene Depends on the Cell Type Targeted

153 citations , April 1998 in “Current Biology”

The risk of skin tumors becoming malignant depends on the specific skin cell type affected.

research Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage

441 citations , May 1996 in “Journal of Cell Science”

This study evaluated keratin 19 (K19) as a marker for skin stem cells, using a mouse model to identify these cells as [3H]thymidine-label-retaining cells. K19 was found to be a marker for skin stem cells in hair follicles, with expression varying by body site, donor age, and culture time. K19 was present in hair follicles but absent in interfollicular epidermis at hairy sites, while at glabrous sites, K19-positive cells were located in deep epidermal rete ridges. The study found a higher proportion of K19-positive cells in newborn foreskins compared to older ones, correlating with the variation in keratinocyte culture lifespan and potentially explaining why children heal faster than adults. The findings suggested that K19 expression could be a valuable tool for characterizing skin stem cells in various conditions.