1. ^*Department of Dermatology Champagne-Ardenne, France
2. ^†Department of Biochemistry, CNRS FRE 2534 Faculty of Medicine Champagne-Ardenne, France
3. ^‡Laboratory Pol Bouin CHU–Reims, INSERM 514, IFR 53 Biomolecules, University of Reims, Champagne-Ardenne, France

Correspondence: Philipe Bernard, Service de Dermatologie, Hôpital Robert Debré, Avenue du General Koenig, 51092 Reims Cedex, France Email: pbernard@chu-reims.fr

Received 27 June 2003; Revised 12 September 2003; Accepted 15 September 2003; Published online 12 February 2004.

Abstract

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 -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.