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Updated: Jul 15, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
CD34 expression by hair follicle stem cells is required for skin tumor development in mice
Carol S Trempus1, Rebecca J Morris, Matthew Ehinger
1Cancer Biology Group, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. trempus@niehs.nih.gov
Abstract:
The cell surface marker CD34 marks mouse hair follicle bulge cells, which have attributes of stem cells, including quiescence and multipotency. Using a CD34 knockout (KO) mouse, we tested the hypothesis that CD34 may participate in tumor development in mice because hair follicle stem cells are thought to be a major target of carcinogens in the two-stage model of mouse skin carcinogenesis. Following initiation with 200 nmol 7,12-dimethylbenz(a)anthracene (DMBA), mice were promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Under these conditions, CD34KO mice failed to develop papillomas. Increasing the initiating dose of DMBA to 400 nmol resulted in tumor development in the CD34KO mice, albeit with an increased latency and lower tumor yield compared with the wild-type (WT) strain. DNA adduct analysis of keratinocytes from DMBA-initiated CD34KO mice revealed that DMBA was metabolically activated into carcinogenic diol epoxides at both 200 and 400 nmol. Chronic exposure to TPA revealed that CD34KO skin developed and sustained epidermal hyperplasia. However, CD34KO hair follicles typically remained in telogen rather than transitioning into anagen growth, confirmed by retention of bromodeoxyuridine-labeled bulge stem cells within the hair follicle. Unique localization of the hair follicle progenitor cell marker MTS24 was found in interfollicular basal cells in TPA-treated WT mice, whereas staining remained restricted to the hair follicles of CD34KO mice, suggesting that progenitor cells migrate into epidermis differently between strains. These data show that CD34 is required for TPA-induced hair follicle stem cell activation and tumor formation in mice.
Insights
CD34 is essential for hair follicle stem cell activation and mouse skin tumor formation. CD34 knockout mice showed impaired tumor development, highlighting CD34
Area of Science:
- Dermatology and carcinogenesis research.
- Stem cell biology and cancer development.
Background:
- CD34 marks mouse hair follicle bulge stem cells, known for quiescence and multipotency.
- Hair follicle stem cells are potential targets for carcinogens in skin cancer models.
Purpose of the Study:
- To investigate the role of CD34 in skin tumor development using CD34 knockout mice.
- To test if CD34 is required for carcinogen-induced hair follicle stem cell activation and tumor formation.
Main Methods:
- Utilized a two-stage mouse skin carcinogenesis model with 7,12-dimethylbenz(a)anthracene (DMBA) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion.
- Administered varying doses of DMBA and analyzed tumor development, latency, and yield in wild-type (WT) and CD34 knockout (KO) mice.
- Assessed DNA adducts, epidermal hyperplasia, hair follicle cycling (telogen/anagen), and progenitor cell marker (MTS24) localization.
Main Results:
- CD34KO mice failed to develop tumors at lower DMBA doses and showed reduced tumor yield and increased latency at higher doses compared to WT mice.
- CD34KO skin exhibited sustained epidermal hyperplasia, but hair follicles remained in telogen, with retained bulge stem cells.
- MTS24 staining patterns differed, indicating altered progenitor cell migration in CD34KO mice.
Conclusions:
- CD34 is crucial for activating hair follicle stem cells in response to TPA.
- CD34 plays a necessary role in the formation of skin tumors induced by chemical carcinogens in mice.
