CONICET | Buscador de Institutos y Recursos Humanos

Angiogenesis is critical for tumor progression. We previously demonstrated that galectin-1(Gal-1), controls tumor growth by favoring tumor-immune escape. The aim of this 3study was to investigate the role of Gal-1 in the control of tumor angiogenesis. Targeted inhibition of gal-1 gene expression inhibited the formation of new blood vessels and suppressed tumor growth in vivo (p<0,05). Expression of Gal-1 in Kaposi cells (KS) was found to be up-regulated under hypoxic conditions, both in vitro and in vivo. This up-regulated expression was dependent on NF-kB but not on HIF-1a activity (p<0.05). Moreover, conditioned medium from KS hypoxic cells was more effective at inducing tubulogenesis and invasion of endothelial cells (p<0.05). This effect was abrogated when KS cells were infected with shRNA-gal-1 (p<0.01). This result was confirmed in vivo using matrigel plugs assay (p<0.05). Gal-1 bound preferentially to N-glycan residues on HUVEC cells in a dose-dependent manner and promoted tubulogenesis, proliferation and migration/invasion through binding to VEGF receptor 2 (p<0.05). A mechanistic analysis revealed an increase in phosphorylated-Akt and Erk½ following Gal-1 treatment. Our results suggest that hypoxia-regulated Gal-1 is a key modulator of tumor angiogenesis. In addition, we propose a model in which Gal-1 regulated by hypoxia is secreted to the extracellular milieu to regulate angiogenesis and tumor-immune escape, thus influencing tumor progression.