A Novel Mechanism for the Pathogenesis of Nonmelanoma Skin Cancer Resulting from Early Exposure to Ultraviolet Light
Annual rept. 1 Sep 2012-31 Aug 2013
MINNESOTA UNIV MINNEAPOLIS
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We proposed that skin egress, entering the circulation, and traveling throughout the body may be a characteristic of skin stem cells in response to ultraviolet light. We have made four significant findings in this regard 1 murine epidermal keratinocytes migrate preferentially in vitro to whole living bone marrow with its conditioned medium, 2 keratinocytes migrate towards SDF1 alpha and HMGB1 baits over control attractants such as 3T3, medium without serum, and FBS, 3 CD184 SDFR1 alpha is expressed on approximately 27 of CD49fCD34 hair follicle stem cells and suggesting that these cells may have the capacity to follow an SDF1alpha chemokine gradient, and 4 there is an increase in CD49fKeratin 14 cells in blood and bone marrow following solar UV treatment as determined by FACS, immunofluorescence microscopy, and quantitative real-time PCR. The significance of these findings support our hypothesis that 1 skin egress may be a characteristic of skin stem cells in response to ultraviolet light, and 2 bone marrow may be a long-lived reservoir of sunlight initiated stem cells that can repopulate the skin even years later upon damage caused by petrochemicals, skin wounding, or physical, chemical, or thermal damage to the skin.
- Medicine and Medical Research