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CD34 EXPRESSION BY HAIR FOLLICLE STEM CELLS IS REQUIRED FOR SKIN TUMOR DEVELOPMENT IN MICE
Citation:
TREMPUS, C. S., R. J. MORRIS, M. EHINGER, A. ELMORE, C. D. BORTNER, M. ITO, G. COTSARELIS, J. G. NIJHOF, J. PECKHAM, N. FLAGLER, G. KISSLING, M. M. HUMBLE, L. C. KING, L. D. ADAMS, D. DESAI, S. AMIN, AND R. W. TENNANT. CD34 EXPRESSION BY HAIR FOLLICLE STEM CELLS IS REQUIRED FOR SKIN TUMOR DEVELOPMENT IN MICE. Cancer Research. American Association for Cancer Research, Inc., Philadelphia, PA, 67(9):4173-4181, (2007).
Impact/Purpose:
to show that a cell surface protein called CD34 is required for skin tumor formation in mice
Description:
We used knockout mice to show that a cell surface protein called CD34 is required for skin tumor formation in mice. Wild type mice treated with 7-12-Dimethylbenz(a)anthracene (DMBA) and a tumor promoter developed papillomas. When we treated CD34 knockout (KO) mice the same way, no tumors were formed, even though DNA adduct analysis of DMBA-initiated CD34KO keratinocytes revealed that DMBA was metabolically activated into carcinogenic diol epoxides.
Initiated skin retains the ability to form papillomas even with long intervals between carcinogen exposure and tumor promotion. Epidermal stem cells in the hair follicle bulge region are preserved over the life of the animal through many hair follicle generations. It has been suggested that hair follicle epidermal stem cells are the carcinogen target cells that give rise to a population of latent, neoplastic cells. Since CD34 is expressed on the surface of these cells, we tested the hypothesis that CD34 is required for tumor development.
Our studies demonstrated that epidermal stem cell activation mediated by CD34 is necessary for epithelial carcinogenesis in mouse skin. These findings underscore the potential contribution of stem cells to skin carcinogenesis. This basic research into the molecular biology of tumor initiation and promotion using a model chemical demonstrates that cell surface proteins may define cellular susceptibility for carcinogenesis. This could lead to further research to identify whether this observation is also applicable to humans and to other carcinogens.