Inducible Cutaneous Inflammation Reveals a Protumorigenic Role for Keratinocyte CXCR2 in Skin Carcinogenesis

The study demonstrated that in transgenic mice overexpressing PKCα in the epidermis, CXCR2 played a significant role in skin carcinogenesis. When these mice were treated with DMBA and a low dose of TPA, 58% developed skin papillomas that progressed to carcinoma, unlike wild-type mice. The research showed that CXCR2 is expressed by keratinocytes and that its ligands are induced by oncogenic ras and TPA exposure. CXCR2 was crucial for the migration and tumorigenic potential of ras-transformed keratinocytes, as it activated the ERK and Akt pathways. The findings suggested that CXCR2 activation in keratinocytes had both promigratory and protumorigenic effects, contributing to tumor development through autocrine and paracrine pathways.