Role of ADAM-15 in wound healing and melanoma development.

Proteins of the a disintegrin and metalloprotease (ADAM) family are transmembrane proteins involved in ectodomain shedding and in cellular interactions. In skin, ADAM-15 is detected in the epidermis and dermal vascular structures by immunolocalization. Expression is also detected in isolated fibroblast, keratinocytes and endothelial cells in culture. Despite high expression of ADAM-15 throughout the wound repair process, wound healing experiments in vivo revealed a dispensable role of ADAM-15 for the healing process. No alterations in wound closure, re-epithelialization, contraction, scar formation and angiogenesis were detected in animals carrying ADAM-15-/- deletion. When analysing melanoma development by grafting melanoma cells into the flank of ADAM-15-/-, no significant alteration in tumor growth was detected. However, at later stages, melanomas in the ADAM-15-/- animals were smaller than those grown in WT animals. At all time points, no significant differences in vascularization of the peritumoral stroma and tumors were detected. Interestingly, we could detect a reduced number of metastasized lungs and lymph nodes in ADAM-15-/- animals as compared to control littermate mice. In conclusion, our study indicated that ADAM-15 is dispensable for cutaneous wound healing and B16F1 melanoma growth, but significantly contributes to metastasis formation.