Targeting galectins in the tumor endothelium. (A) In quiescent ECs, the specific set of galectins, their expression level, and their cellular localization is represented by a “galectin code.” Having this galectin code, the ECs are angiogenically inactive, the immune surveillance is not impaired, and heterotypic cell adhesion of circulating cells is hampered. The net result is an environment that does not promote tumor progression. (B) In the presence of stimulatory growth factors, the ECs become activated, causing alterations in the repertoire, expression level, and even localization of galectins. This change in the galectin code enhances the angiogenic potential of the cells, hampers a proper immune response, and facilitates metastasis formation. Consequently, the tumor progression potential is high. From this, it can be speculated that changing the galectin code (eg, by altering galectin expression levels or by directly targeting the galectins with blocking antibodies or peptides), a combination of effects could be generated. This might involve inhibition of angiogenesis, reversal of EC anergy, and/or prevention of metastasis formation. Thus, the progressive phenotype of any tumor might be reversed by targeting the galectins that are present on the ECs.