In malignant melanoma, an induced expression compared to melanocytes andpromigratory functionsof APN could be confirmed. Moreover,an epigenetic regulatory mechanism by DNA methylation of the myeloid APN promoter could be recorded. UCHL1-positive melanoma cells were characterized by improved proliferation rates and altered resistance against reactive oxygen species (ROS) damage by interfering with signal transduction pathways. APN and UCHL1 might serve as interesting protein candidates for the generation and establishment of new therapy forms for the treatment of malignant melanoma patients. In anin vitro-transfection model,an inhibitory potential of the APN enzyme activity on cellular proliferation as well as on the migratory capability of CXCR4-positive cells to the corresponding chemoattractiveligandwas demonstrated. Since APN and CXCR4 are involved in tumorigenesis, a better understanding of the molecular mechanisms will be of particular therapeutic interest.Furthermore, a strong colocalization of APN with Fcγ receptors in monocytes could be verified which represents a new functional signal transduction complex.