The elastin connection and melanoma progression

Abstract

Matrikines, i.e. matrix fragments with cytokine-like properties, have been ascribed a major role in regulating tumour progression. The invasive front of melanoma is characterised by intense fragmentation of dermal elastic fibres. Elastase-mediated elastolysis liberates elastin fragments, i.e. elastokines, that stimulate several aspects of melanoma progression such as to enhance melanoma cell invasion through type I collagen or increase angiogenesis. Induced-membrane-type 1 metalloprotease (MT1-MMP) expression following elastin receptor (S-Gal) occupancy by elastokines is responsible for those biological activities. Several matrix-derived peptides with a GXXPG consensus sequence adopting a type VIII beta-turn conformation were as potent as elastokines in promoting angiogenesis in a Matrigel assay, and galectin-3 also contains several similar repeats within its N-terminal domain. We propose that S-Gal might constitute a novel therapeutic target for controlling melanoma progression.