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Cutaneous melanoma is a highly malignant tumor type which is characterized by its tendency to give rise to metastases. Stromal relationships are essential for growth and metastasis of solid tumors. In cutaneous melanoma, microscopic level of invasion (Breslow index), overall architecture of cells (horizontal or vertical growth phase), angiogenesis, vessel invasion are morphological features which may carry prognostic significance. As demonstrated by in vivo studies, stromal reaction in melanoma is mainly characterized by collagen and elastin proteolysis preferentially localized around the tumor at the invasive front along with variable angiogenesis and lymphocyte infiltration. On the basis of recent findings, it becomes increasingly evident that resident stromal cells (fibroblasts, endothelial cells) are implicated in the metastatic process, including proliferation, matrix degradation, or migration of melanoma cells through cell-cell cross-talk by soluble factors (proteases, cytokines, growth factors) or by direct contact.

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.