Figure 1. Association of Gal1 with complex N-gycans on VEGFR2 compensates for the absence of cognate ligand in anti-VEGF refractory tumors. In response to VEGF blockade, anti-VEGF refractory tumors (upper pannel) secrete higher amounts of Gal1 and their associated endothelial cells (ECs) express all the repertoire of glycans that are critical for Gal1 binding (increased β1,6 N-glycan branching, augmented poly-N-acetyllactosamine extension and lower α2,6 sialylation). This inducible EC glycophenotype facilitated Gal1 signaling, compensatory angiogenesis and tumor growth. In contrast, blood vessels associated with anti-VEGF sensitive tumors (lower panel) displayed higher amounts of α2,6-linked sialic acid which prevented Gal-1-VEGFR2 interactions.