Distinctive glycosylation signature and galectin-1 expression in dierent human breast cancer lines (BCC) and tissues

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

Mar del Plata

Congreso; SAIC/SAI/SAFE 2016; 2016

Galectins can inuence antitumor immune response, angiogenesis and tumor metastasis by interacting with cell surface glycans. Changes in glycosylation observed in malignant cells are specically sensed by lectins and can be used as disease biomarkers. With the goal of investigating the relevance of galectin-glycan interactions in shaping distinct breast cancer phenotypes, we rst selected ve human cell lines that model dierent human breast cancer types. To identify specic glycan structures, we used a panel of biotinylated lectins (Galectin-1 (Gal1), LEL, SNA, PNA, PHA-L and MAA) and analyzed their binding to the cell surface by ow cytometry. We found that highly aggressive lines, as the triple negative MDA-MB- 231 and the HER2-enriched Trastuzumab (TZ)-resistant JIMT-1, showed higher binding of Gal1 (p<0.001) and MAA (p<0.01) than SKBR3, BT474 (Her2 + /TZ-sensitive) and T47D (Luminal A) indicating abundant terminal LacNAc residues and higher 2-3 sialylation. MDA-MB-231 also stained positively for LEL (p<0.05) and PNA (p<0.05), reecting abundant poly-LacNAc extensions and asialo-core 1-O-glycans. In contrast, BT-474 cell line exhibited higher binding of SNA (p<0.05) indicating enrichment of 2-6-linked sialic acid, correlating with a restrictive Gal1 binding phenotype (p<0.001). Remarkably, Western blot analysis showed that TZ-resistant JIMT-1 expressed higher levels of Gal1 in comparison to its TZ-sensitive counterparts: SK-BR-3 and BT-474 (p<0.001). In addition, T47D and MDA-MB- 231 cell lines also showed substantial Gal1 expression. Finally, lectin histochemistry in paran embedded human breast cancer sections revealed a diverse binding of Gal1 and SNA in stroma and epithelial cells, reecting heterogenous glycan patterns among patients. We conclude that each breast cancer cell line and tissue has a particular ?glycosylation signature? that, in association with Gal-1 expression levels, may predict cancer progression or response to targeted therapies.