These results show, for the first time, that targeted inhibition of MMP-1, a single effector of the Raf/MEK/ERK signaling cascade, prevents the progression of melanoma from a primary to metastatic tumor and, as such, may represent a useful therapeutic tool in controlling this disease.
Thus, these results suggest that MMP-1 produced from melanoma cells would play a role in tumor progression by both degrading matrix proteins and generating active growth factors such as TGF-beta in vivo.
Taken together, our results indicate an essential role for soluble factors, mainly IL-1alpha and bFGF, in the stimulation of dermal fibroblasts by human melanoma cells to secrete MMP-1.