Elastin-derived peptides upregulate matrix metalloproteinase-2-mediated melanoma cell invasion through elastin-binding protein.
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.
Ntayi
Carole
C
Department of Dermatology, CNRS FRE 2534, Faculty of Medicine, University of Reims, Champagne-Ardenne, France.
Labrousse
Anne-Laure
AL
Debret
Romain
R
Birembaut
Philipe
P
Bellon
Georges
G
Antonicelli
Frank
F
Hornebeck
William
W
Bernard
Philipe
P
D002455:Cell Division / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D004549:Elastin / Q000378:metabolism*; D005697:Galactosides / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D008666:Metalloendopeptidases / Q000378:metabolism; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000378:metabolism; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014468:Umbelliferones / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D024042:Collagen Type I; D005697:Galactosides; D010446:Peptide Fragments; D014468:Umbelliferones; C101993:cyclohexenoesculetin-beta-galactoside; D019716:Tissue Inhibitor of Metalloproteinase-2; D004549:Elastin; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2