Spatially controlled induction and regression of basal cell carcinoma, visualized by serial imaging in young and old...

Basal cell carcinoma (BCC) is the most common skin malignancy, and the risk of developing BCC increases with age. BCC results from dysregulated Hedgehog signaling leading to activation of GLI transcription factors. In this study, we examined the impact of aging on BCC in cohorts of young (n = 37) versus aged (n = 97) mice using a transgenic mouse model in which GLI2A (GLI2 activator) was induced in mice at either the age of 7 weeks or 22-24 months, and BCC tumor development was monitored by weekly imaging. Young mice developed tumors slightly sooner and in greater numbers than aged mice but demonstrated similar growth rates once tumors appeared. However, BCC-associated increases in blood vessel diameter, tortuosity, and ulceration were impacted by age. BCCs in both young and aged mice underwent similarly rapid regression after GLI2A transgene inactivation. Taken together, our findings reveal that aging affects tumor-associated vasculature but not BCC formation or regression in our model. These results are in keeping with the notion that a major contributor to the increased incidence of BCCs in elderly patients is the accumulation of oncogenic driver mutations over time rather than intrinsic changes in aged skin that promote BCC tumorigenesis.