GLYCOSYLATION-DEPENDENT ALCAM-GALECTIN-8 INTERACTIONS MEDIATE MDA-MB-231 BREAST CANCER CELL ADHESION

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

BUENOS AIRES-Universidad de San Martin, Buenos Aires, Argentina May 8-10, 2019

Simposio; 3rd GLYCOAR SYMPOSIUM; 2019

GLYCOAR- Argentinian Glycobiology Consortium

P28. Glycosylation-dependent ALCAM-Galectin-8 interactionsmediate MDA-MB-231 breast cancer cells adhesionCagnoni, AJ; Ferragut, F; Colombo, LL; Sánchez Terrero, C;Wolfenstein-Todel, C; Troncoso, MF; Vanzulli, SI; Rabinovich,GA; Elola, MT; Mariño, KV.E-mail address: alejandrojcagnoni@gmail.comTriple negative breast cancer represents 15% of all breast cancersand is characterized by a very aggressive behavior, a scenario inwhich effective treatments for patients are still lacking. Galectin-8(Gal-8), a tandem-repeat-type galectin, has been described as amodulator of cellular functions including adhesion, apoptosis,pathogen recognition, autophagy, and immunomodulation.Activated leukocyte cell adhesion molecule (ALCAM), a receptorfor endogenous Gal-8, is a member of the immunoglobulinsuperfamily involved in cell-cell adhesion. In this work, we exploredALCAM-Gal-8 interactions and their physiologic relevance in triplenegative 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 ofcomplex 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 corefucosylated structures represented only 30% of complex N-glycanstructures. The N-glycosylation profile of ALCAM in MDA-MB-231cells resulted permissive for Gal-8 binding, and neuraminidasedigestion considerably increased the number of structuresrecognized by this lectin. Furthermore, we found that cell sialylationis a key factor for Gal-8-mediated cell adhesion, as neuraminidasetreatment of MDA-MB-231 significantly increased cell adhesiononto Gal-8-coated surfaces. Altogether, these findingsdemonstrate an important role for cell sialylation and, in particular,ALCAM sialylation in modulating MDA-MB-231 cell adhesion ontoGal-8-coated surfaces.