INVESTIGADORES
RABINOVICH Gabriel Adrian
congresos y reuniones científicas
Título:
DISSECTING THE ROLE OF EXTRACELLULAR GALECTIN-1 IN THE REGULATION OF NEOVASCULARIZATION
Autor/es:
D. CROCI; M. SALATINO; N. RUBINSTEIN; M. TOSCANO; J. ILARREGUI; G. BIANCO; L. CAMPAGNA; G. RABINOVICH
Lugar:
RIO DE JANEIRO
Reunión:
Congreso; 13TH INTERNATIONAL CONGRESS OF IMMUNOLOGY; 2007
Institución organizadora:
ICI 2007
Resumen:
Dissecting the role of extracellular galectin-1 in the regulation of neovascularization 1D.O. Croci, 1M. Salatino, 1N. Rubinstein, M.A. Toscano, J.M. Ilarregui, G.A. Bianco, L. Campagna, G.A. Rabinovich 1Laboratorio de Inmunogenética, Htal. de Clínicas “José de San Martín”, Facultad de Medicina, UBA. Angiogenesis is a critical process for tumor progression. We previously demonstrated that galectin-1, a glycan-binding protein with immunosuppressive activity, controls tumor growth by favoring tumor-immune escape and promoting angiogenesis in a model of Kaposi Sarcoma. The present study was focussed on dissecting the mechanisms underlying the proangiogeneic effects of galectin-1. Recombinant galectin-1 bound human umbilical vascular endothelial cells (HUVEC) in a dose-dependent manner. This effect was carbohydrate-dependent since it was prevented by lactose,a specific disaccharide (p<0.01). Moreover, treatment of HUVEC cells with recombinant galectin-1 promoted tubulogenesis (p<0.01) and proliferation (p<0.05). A mechanistic analysis of the intracellular signals involved in this effect revealed a pronounced increase in phosphorylated-Akt and Erk½ following galectin-1 treatment To evaluate the relevance of MAPK and PI3K/Akt pathways in galectin-1-induced angiogenesis we analyzed the requirement of these pathways for endothelial tubule-like formation and proliferation. Pretreatment of HUVEC with either PI3K-inhibitor LY294.002 (2mM) or Erk1/2-inhibitor U0126 (5mM) abolished the ability of galectin-1 to induce tubulogenesis (p<0.01) and proliferation (p<0.05). Finally, expression of galectin-1 in human Kaposi sarcoma cells was found to be strongly up-regulated under conditions of profound hypoxia, the main proangiogenic stimulus. Our results suggest that hypoxia-regulated galectin-1 is a key modulator of tumor cell angiogenesis by promoting tubulogenesis and proliferation of endothelial cells through ERK1/2 and PI3K/Akt-dependent pathways. Thus galectin-1 present in the tumor microenvironment, not only regulates tumor-immune escape but also controls other critical events in tumor progression including cell migration and angiogenesis. Whether these events are interconnected still remains to be elucidated.