N-GLYCAN-LECTIN AXIS MODULATES RESPONSE TO TRASTUZUMAB THERAPY IN HER2+ BREAST CANCER CELL LINES

SALATINO M ; CAGNONI A; RABINOVICH GA; DALOTTO-MORENO T; MARIÑO KV; PERROTTA RM

Congreso; Reunion Conjunta de las Biociencias; 2017

Galectins decode glycan-containing information in surface cell 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 cellular functions. Tumors produce high amount of Gal-1 evading immune response and promoting aberrant angiogenesis. In this work, we explore the HER2+ breast cancer glycan profile and investigate whether Gal-1 may bind to ErbB2 mediating resistance to anti-HER2 targeted therapies such as Trastuzumab (TZ). Previously we demonstrated by lectin binding assay and N-glycome profiling by WAX-HPLC that TZ-resistant JIMT-1 cells exhibited a Gal-1 permissive glycophenotype. Here, we analyzed the expression of galectins and glycosyltranferases essential for biosynthesis of Gal-1 ligands. We found that JIMT-1 TZ resistant cell line expressed higher levels of Gal-1 (p