N-glycan lectin axis/framework modulates response to trastuzumab therapy in HER2+ breast cancer cell lines

PERROTTA, RAMIRO; DALOTTO MORENO, TOMAS; CAGNONI, ALEJANDRO J; MARIÑO, KARINA V.; CROCI, DIEGO O.; RABINOVICH, GABRIEL A.; SALATINO, MARIANA

Buenos Aires

Conferencia; Reunión Sociedad Argentina de Biociencias 2017; 2017

Sociedad Argentina de Inmunología

Galectins decode glycan information contained in cell surface receptors. In particular, Galectin-1 (Gal-1), binds to terminal LacNAc residues on glycosylated proteins in the absence of α2-6 sialic acid capping, modulating several cellular functions. Tumors secrete Gal-1 to evade immune responses and to promote aberrant angiogenesis. In this work, we explored the glycan profile of HER2+ breast cancer cell lines and investigated whether Gal-1 could mediate resistance to anti-HER2 targeted therapies such as Trastuzumab (TZ). Previously, we demonstrated by lectin-binding assay and WAX-UPLC that TZ-resistant JIMT-1 cells exhibited a Gal-1 permissive glycophenotype. Herein, we analyzed the expression of galectins and glycosyltranferases essential for biosynthesis of Gal-1 ligands. We found that the JIMT-1 TZ resistant cell line expressed higher levels of Gal-1 than its sensitive counterparts (BT474 and SKBR3) both at the mRNA (p