Targeted expression of tumor necrosis factor-related apoptosis-inducing ligand TRAIL in skin protects mice against chemical carcinogenesis

BACKGROUND: Gene ablation studies have revealed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L, TNFSF10) plays a crucial role in tumor surveillance, as TRAIL-deficient mice exhibit an increased sensitivity to different types of tumorigenesis. In contrast, possible tumor-protective effect of increased levels of endogenous TRAIL expression in vivo has not been assessed yet. Such models will provide important information about the efficacy of TRAIL-based therapies and potential toxicity in specific tissues. METHODS: To this aim, we engineered transgenic mice selectively expressing TRAIL in the skin and subjected these mice to a two-step chemical carcinogenesis protocol that generated benign and preneoplastic lesions. We were therefore able to study the effect of increased TRAIL expression at the early steps of skin tumorigenesis. RESULTS: Our results showed a delay of tumor appearance in TRAIL expressing mice compared to their wild-type littermates. More importantly, the number of tumors observed in transgenic animals was significantly lower than in the control animals, and the lesions observed were mostly benign. Interestingly, Wnt/β-catenin signaling differed between tumors of wild-type and TRAIL transgenics. CONCLUSION: Altogether, these data reveal that, at least in this model, TRAIL is able on its own to act on pre-transformed cells, and reduce their tumorigenic potential.