Transglutaminase-mediated oligomerization of galectin-3 modulates human melanoma cell interactions with laminin.
Tumor cell adhesion and migration to laminin are important events during invasion and metastatic spread. Galectin-3, a multifunctional member of the galectin family, binds specifically the poly-N-acetyllactosamine residues of laminin and has been implicated in tumor invasion and metastasis. Galectin-3 is multimerized by transglutaminase, an enzyme that catalyzes cross-linking between glutamine and other aminoacid residues. In this study, we examined the consequences of transglutaminase-mediated galectin-3 oligomerization on the interactions between cancer cells and laminin. We first demonstrated that human galectin-3 is cross-linked by guinea pig liver transglutaminase, forms oligomers, and incorporates the marker 5-(biotinamido) pentylamine. Expression of transglutaminase activity in the A375 and A2058 human melanoma cell extracts was revealed by its ability to induce galectin-3 oligomerization and 5-(biotinamido) pentylamine incorporation. Transglutaminase-treated galectin-3 did not affect adhesion or migration of the melanoma cells to laminin but consistently induced a significant increase of the percentage of cell spreading compared to the control (23.5 +/- 2.3%, vs. 10.6 +/- 1.9% at 180 min, p < 0.05), or to untreated galectin-3 or transglutaminase alone. Our study is the first demonstration that human galectin-3 is oligomerized by transglutaminase with, as a consequence, a specific effect of melanoma cell spreading on laminin. This phenomenon could be of significance in the modulation of cancer cell interactions with laminin during tumor invasion and metastasis.
van den Brûle
F A
FA
Metastasis Research Laboratory, University of Liège, Belgium. f.vandenbrule@chu.ulg.ac.be
Liu
F T
FT
Castronovo
V
V
D000588:Amines / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism* / Q000494:pharmacology; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D002846:Chromatography, Affinity; D019281:Dimerization; D037502:Galectin 3; D006168:Guinea Pigs; D006801:Humans; D007785:Lactose / Q000378:metabolism; D007797:Laminin / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008545:Melanoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D015335:Molecular Probes / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000588:Amines; D000943:Antigens, Differentiation; D037502:Galectin 3; D007797:Laminin; D015335:Molecular Probes; D011994:Recombinant Proteins; C076022:5-(biotinamido)pentylamine; D001710:Biotin; D011503:Transglutaminases; D007785:Lactose