Glycosylation-dependent ALCAM-Galectin-8 interactions mediate MDA-MB-231 breast cancer cell adhesion

CAGNONI, ALEJANDO J.; FERRAGUT, FÁTIMA; COLOMBO, LUCAS L.; SÁNCHEZ TERRERO, CLARA; WOLFENSTEIN-TODEL, CARLOTA; TRONCOSO, MARÍA F.; VANZULLI, SILVIA I.; RABINOVICH, GABRIEL A.; ELOLA, MARÍA T.; MARIÑO, KARINA V.

Buenos Aires

Simposio; 3rd Argentinean Symposium of Glycobiology; 2019

Triple negative breast cancer represents 15% of all breast cancers and is characterized by a very aggressive behavior, a scenario in which effective treatments for patients are still lacking. Galectin-8 (Gal-8), a tandem-repeat-type galectin, has been described as a modulator of cellular functions including adhesion, apoptosis, pathogen recognition, autophagy, and immunomodulation.Activated leukocyte cell adhesion molecule (ALCAM), a receptor for endogenous Gal-8, is a member of the immunoglobulin superfamily involved in cell-cell adhesion. In this work, we explored ALCAM-Gal-8 interactions and their physiologic relevance in triple negative breast cancer. We found that ALCAM silencing in MDAMB-231 breast cancer cells decreases cell adhesion and migrationonto Gal-8-coated surfaces in a glycan-dependent manner. ALCAM N-glycome analysis revealed a major proportion of complex N-glycans, with prevalent bi- or tri-antennary structures, presented no sulfation and around 30% of sialylated structures. Moreover, no antenna fucosylation was detected and core fucosylated structures represented only 30% of complex N-glycan structures. The N-glycosylation profile of ALCAM in MDA-MB-231 cells resulted permissive for Gal-8 binding, and neuraminidase digestion considerably increased the number of structures recognized by this lectin. Furthermore, we found that cell sialylation is a key factor for Gal-8-mediated cell adhesion, as neuraminidasetreatment of MDA-MB-231 significantly increased cell adhesion onto Gal-8-coated surfaces. Altogether, these findings demonstrate an important role for cell sialylation and, in particular, ALCAM sialylation in modulating MDA-MB-231 cell adhesion onto Gal-8-coated surfaces.