A recent study (Nature 507, 109–113, 2014) has found that ultraviolet (UV) radiation promotes melanoma progression by creating an inflammatory microenvironment that fosters metastatic spread.

Credit: Dr. Cecil H. Fox / Science Source

UV exposure is known to underscore the mutational profile of melanoma cells. However, using a genetically engineered mouse model of melanoma, the authors observed that UV radiation–induced damage of normal keratinocytes caused an inflammatory response that has more effect on metastatic progression than on primary tumor growth.

The authors unravel a role for the innate immune system in sensing this UV-induced DNA damage. Irradiated keratinocytes release the nuclear protein HMGB1, which serves as a chemoattractant for neutrophils. In turn, neutrophils secrete factors that promote angiogenesis and angiotropic growth of melanoma cells, contributing to their spread.

The relevance of the findings to human disease, as well as their therapeutic application, needs further exploration, but the authors were able to show that ulcerated tumors, or those with evident neutrophil infiltration, bear a higher risk of metastasis. This suggests that the metastasis mechanism uncovered in the study plays a role in the context of UV-induced skin tumorigenesis in humans.