095 Fibroblast alterations during cutaneous skin cancer development

Cutaneous basal (BCC) and squamous cell carcinomas (SCC) are the most commonly occurring cancers in humans. These skin driven by DNA damage to epidermis, body’s outermost protective barrier. Our previous studies demonstrate that damaging agents activate inflammasome signaling dermal fibroblasts, which enhances epithelial proliferation plasticity wild-type characteristics associated with tumorigenesis. Strikingly, however, role of fibroblasts cutaneous cancer development has not been adequately addressed. Cancer-associated (CAFs) predominant tumor stroma have proposed drive progression many cancers, including BCC SCC. However, direct CAFs initiation is currently unknown. In this study, we collected primary human specimens analyze alterations SCC tumors compared from normal tissue. We noted striking morphological changes both CAFs, had redistributed accumulated near interface. Furthermore, showed evidence activation, overlying epithelium exhibited stem fate mis-specification. Notably, these similar those when exposed agents. data suggest may be coaxed into a pre-CAF-like state upon exposure, CAF promote progression. Future work will test necessity sufficiency tumorigenesis using as well mouse models.