Type I collagen mediates
melanoma cells invasion through upregulation of matrix metalloproteinases-1 and -2 (MMP-1 and -2) expression and activation. We investigated here the contribution of
elastin-derived
peptides (ED), degradation products of
elastin, the main component of elastic fibers in
melanoma cells invasion and MMP-1 and -2 expression. Our results evidenced fragmentation of
elastin at the invasive front of
melanoma, particularly in the most invasive
tumors where those fibers nearly totally vanished. By electron microscopy, elastolysis was found to occur mainly at the periphery of
melanoma cells, where close contact between elastic fibers and cells could be noticed. Therefore, we showed in vitro that plating
melanoma cells high tumorigenic potential on ED-coated dishes, selectively enhanced MMP-2, as membrane-type MMP-1 (MT1-MMP) production and activation. Nevertheless,
pro-MMP-2 activation was not observed owing to the parallel increase in
tissue inhibitor of metalloproteinase (TIMP)-2 expression. The effects of ED on
melanoma cells were found to be mediated by splicing form of
beta-galactosidase (
S-Gal) occupancy, as being suppressed by
lactose. Supplementing
collagen lattices with ED led to consistent activation of MMP-2 that can be attributed to
TIMP-2 downregulation. Upregulation of MMP-2 activation by ED led to enhanced
melanoma cells invasion through
S-Gal occupancy. Immunohistochemistry studies, confirmed that
S-Gal expression was more prominent at the
melanoma invasion site associated with a strong expression of MMP-2 and
MT1-MMP. We hypothesize that ED following interactions with
S-Gal elastin receptor can favor
melanoma cells invasion through a three-dimensional
type I collagen matrix by upregulating MMP-2 activation.