Antifibrogenic effects of B16 melanoma-conditioned medium

Abstract

BACKGROUND:Some malignant cancers show high levels of local invasiveness by the secretion of soluble factors that can degrade adjacent tissues and suppress surrounding cell growth. We investigated the possibility of treating fibroproliferative scars based on these properties of malignant melanoma. MATERIAL AND METHODS:B16 melanoma-conditioned medium (B16 M-CM) was added to keloid fibroblasts (KFs), and proliferation, migration, and type I collagen production were measured. The cell cycle and signaling pathways were also analyzed. Proteins associated with cell proliferation were measured with Western blot analysis. Animal experiments using a rabbit ear model was performed to confirm the effect of B16 M-CM in vivo. RESULTS:B16 M-CM reduced proliferation, migration, and type I collagen production of KFs. This treatment also increased the number of cells in the subG1 phase and decreased phosphorylation levels of AKT, extracellular signal-regulated kinase1/2, cyclin D1, and c-Myc of KFs. Additionally, B16 M-CM reduced the thickness of rabbit ear scars in the rabbit ear model in vivo. CONCLUSIONS:B16 M-CM can suppress proliferation, migration, and type I collagen production of KFs. In addition, concentrated B16 M-CM reduced scar thickness in the rabbit ear model. The specific proteins involved should be identified in a future study.