Structural Superimposition

Abstact

Glioblastoma (GBM) is a fast-growing and aggressive primary brain tumor with an average survival time of 12-18 months. GBM growth and invasion rely on multiple and dynamic signaling events in the tumor microenvironment, in which several glycan-binding proteins act as essential mediators. Among them, galectin-3 (Gal-3) plays a key role in cell-cell and cell-extracellular matrix communication. Gal-3 may be inhibited by complex polysaccharides such as pectins, which might reduce GBM aggressiveness and invasiveness. To identify possible interactive mechanisms involving Gal-3, we have selectively modified the structure of pectins extracted fromCampomanesia xanthocarpa Berg to obtain varied GalA:Ara and Gal:Ara ratios along the polysaccharide backbone. The interactive influence of the fully modified structures as well as the individual monosaccharides was monitored by circular dichroism and X-ray diffraction. The impact of all modified pectins on the T98G and U87MG cell viability and Gal-3 expression was also evaluated. Our results suggest that galactose and galacturonic acid may be partly responsible for the protein structural changes. The pectins induced significant cytotoxicity and reduced Gal-3 expression in vitro, suggesting that biomaterials with a similar Gal:Ara ratio may be employed as adjuvants in GBM therapy.