The elastin connection and melanoma progression.
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.
Hornebeck
William
W
UMR 6198 CNRS, IFR 53 Biomolecules, Université de Reims, Reims, France. william.hornebeck@univ-reims.fr
Robinet
Arnaud
A
Duca
Laurent
L
Antonicelli
Frank
F
Wallach
Jean
J
Bellon
Georges
G
D000595:Amino Acid Sequence; D018450:Disease Progression; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011956:Receptors, Cell Surface / Q000378:metabolism
D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; D004549:Elastin; D020782:Matrix Metalloproteinases