A specific sequence of the noncollagenous domain of the alpha3(IV) chain of type IV collagen inhibits expression and activation of matrix metalloproteinases by tumor cells.
The invasive properties of melanoma cells correlate with the expression of matrix metalloproteinases (MMPs) and their physiological modulators (tissue inhibitors of metalloproteinase and membrane-type MMPs) and with that of the alphaVbeta3 integrin. We investigated the effect of anterior lens capsule type IV collagen and of the alpha3(IV) collagen chain on the invasive properties of various tumor cell lines (HT-144 melanoma cells, HT-1080 fibrosarcoma cells). We demonstrated that anterior lens capsule type IV collagen or specifically the synthetic peptide alpha3(IV) 185-203 inhibited both the migration of melanoma or fibrosarcoma cells as well as the activation of membrane-bound MMP-2 by decreasing the expressions of MT1-MMP and the beta3 integrin subunit.
Pasco
S
S
Lab Biochemistry, IFR 53 Biomolecules, CNRS UPRESA 6021, UFR Medicine, Reims, France.
Han
J
J
Gillery
P
P
Bellon
G
G
Maquart
F X
FX
Borel
J P
JP
Kefalides
N A
NA
Monboisse
J C
JC
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D017931:DNA Primers; D004789:Enzyme Activation; D005347:Fibroblasts; D005354:Fibrosarcoma; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism*; D008545:Melanoma; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D019030:Receptors, Vitronectin / Q000096:biosynthesis / Q000235:genetics*; D012867:Skin; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D010446:Peptide Fragments; D019030:Receptors, Vitronectin; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2