Identification of beta1 integrin as mediator of melanoma cell adhesion to lumican.
Lumican is a small leucine-rich proteoglycan (SLRP) present in the dermal extracellular matrix. Previous data from our laboratory demonstrated that lumican decreases melanoma progression in vivo. Here, we show that melanoma cell migration is decreased by lumican and that this effect is due to an enhanced cell adhesion. The adhesion of A375 human melanoma cells on lumican was dose-dependent and required Mg2+ and Mn2+ divalent cations. Using a panel of monoclonal antibodies directed against integrin subunits, we showed that A375 cells can bind to recombinant lumican through beta1 type integrins. Moreover, the use of rhodocetin, an inhibitor of alpha2 integrin, suggested that this particular subunit might also be involved in the interaction with lumican. The increased beta1 integrin-mediated adhesion of melanoma cells to lumican might explain, at least in part, the anti-invasive effect of this SLRP.
D'Onofrio
Marie-France
MF
Laboratoire de Biochimie Médicale et Biologie Moléculaire, CNRS UMR 6198, Faculté de Médecine, IFR 53, Université de Reims-Champagne-Ardenne, 51095 Reims cedex, France.
Brézillon
Stéphane
S
Baranek
Thomas
T
Perreau
Corinne
C
Roughley
Peter J
PJ
Maquart
François-Xavier
FX
Wegrowski
Yanusz
Y
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D011508:Chondroitin Sulfate Proteoglycans / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D007632:Keratan Sulfate / Q000008:administration & dosage*; D000071234:Lumican; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice
D011508:Chondroitin Sulfate Proteoglycans; D019012:Integrin beta1; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D007632:Keratan Sulfate