TRANSGLUTAMINASE-MEDIATED OLIGOMERIZATION OF GALECTIN-3 MODULATES HUMAN-MELANOMA CELL-INTERACTIONS WITH LAMININ

Tumor cell adhesion and migration to laminin are important events duri ng invasion and metastatic spread. Galectin-3, a multifunctional membe r of the galectin family, binds specifically the poly-N-acetyllactosam ine 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 res idues. In this study, we examined the consequences of transglutaminase -mediated galectin-3 oligomerization on the interactions between cance r cells and laminin. We first demonstrated that human galectin-3 is cr oss-linked by guinea pig liver transglutaminase, forms oligomers, and incorporates the marker 5-(biotinamido) pentylamine. Expression of tra nsglutaminase activity in the A375 and A2058 human melanoma cell extra cts was revealed by its ability to induce galectin-3 oligomerization a nd 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 per centage 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 transgl utaminase alone. Our study is the first demonstration that human galec tin-3 is oligomerized by transglutaminase with, as a consequence, a sp ecific effect of melanoma cell spreading on laminin. This phenomenon c ould be of significance in the modulation of cancer cell interactions with laminin during tumor invasion and metastasis.