title: Transglutaminase-mediated oligomerization of galectin-3 modulates human melanoma cell interactions with laminin.
abstract: 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.
authors.affiliation: Metastasis Research Laboratory, University of Liège, Belgium. f.vandenbrule@chu.ulg.ac.be
authors.forename: F A
authors.initials: FA
authors.lastname: van den Brûle
authors.forename: F T
authors.initials: FT
authors.lastname: Liu
authors.forename: V
authors.initials: V
authors.lastname: Castronovo
mesh_terms: 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
chemical_list: 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