Galectin-1, an endogenous lectin involved in tumor-immune escape, links hypoxia and angiogenesis in Kaposi sarcoma DO.

CROCI DO; SALATINO M; RUBINSTIEN N; ILARREGUI JM; TOSCANO MA; A. ALBINI; RABINOVICH GA

Keystone, Colorado, USA

Simposio; Keystone simposia en molecular and celullar biology; 2010

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 study 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 sarcoma (KS) cells 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). These results were 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 increased phosphorylated-Akt and Erk½ following Gal-1 treatment.  Our results suggest that hypoxia-regulated Gal-1 is a key modulator of tumor angiogenesis. Our study suggests that hypoxia-regulated Gal-1 is secreted to the extracellular milieu to regulate angiogenesis and tumor-immune escape, thus influencing tumor progression.