Elevated Ornithine Decarboxylase Activity Promotes Skin Tumorigenesis by Stimulating the Recruitment of Bulge Stem Cells but Not via Toxic Polyamine Catabolic Metabolites

The study investigated the role of elevated ornithine decarboxylase (ODC) activity in skin tumorigenesis, particularly its effect on bulge stem cells and polyamine catabolic metabolites, using ODC-ER transgenic mice. It was found that increased ODC activity promoted skin tumor development by recruiting bulge stem cells, which are associated with hair follicles, rather than through the generation of reactive oxygen species (ROS) by polyamine catabolic oxidases. Inhibiting polyamine catabolic oxidase activity with MDL72527 resulted in a shorter tumor latency, increased tumor burden, and higher conversion to carcinomas, indicating that the tumorigenic effect was not due to ROS generation. The findings suggested that targeting ODC activity could be a potential strategy for preventing skin tumorigenesis by affecting stem cell dynamics rather than through the toxicity of polyamine breakdown products.