Syk Kinase as a Biomarker of Skin UV Damage and Photocarcinogenesis

(E. Papazoglou and J. Uitto)

Abstract: There is no easily accessible molecular indicator of the level of skin UV damage and its correlation to development of skin cancer. Many known changes in matrix metalloproteinases occur only after very prolonged UV exposure and damage and as such are not useful early indicators that could be used as warning signs. Diagnostic histopathological evaluations in the clinic and the efficacy of cosmeceutical skin treatments promoted to protect or repair damage is mainly based on visual subjective comparisons. There is an unmet need to quantify, understand and predict progression of skin damage to skin cancer, and biomarkers that would prove valid indicators can be translated into high volume lab tests and valuable drug targets. This project aims to evaluate the sensitivity and usefulness of Syk (spleen tyrosine kinase) as a ubiquitous biomarker of skin photodamage and photocarcinogenesis.

Our current in vitro studies demonstrated for the first time that Syk kinase enhanced metalloproteinase-1 (MMP-1) expression in human skin fibroblasts in-vitro and hairless mice in-vivo treated with UV radiation. Our results suggest that Syk kinase can play an important role in UV induced photo-damage by affecting MMP-1 expression and is elevated in many common skin cancers. This project will validate Syk-kinase expression as a function of time in animal experiments and evaluate existing skin biopsy samples for Syk expression. If successful, this project could provide valuable targets for diagnosis, prevention and treatment of skin photoaging and photocarcinogenesis.