title: Role of ADAM-15 in wound healing and melanoma development.
abstract: 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.
authors.affiliation: Department of Dermatology and Venerology, University of Cologne, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schönefuß
authors.forename: Anna N
authors.initials: AN
authors.lastname: Abety
authors.forename: Jan
authors.initials: J
authors.lastname: Zamek
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.forename: Paola
authors.initials: P
authors.lastname: Zigrino
mesh_terms: D051722:ADAM Proteins / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000556:secondary; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D018919:Neovascularization, Physiologic; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing
chemical_list: D008565:Membrane Proteins; D051722:ADAM Proteins; C098660:ADAM15 protein, human