Identification of a unique galectin signature during progression of human prostate cancer place galectin-1 as a major target of anti-angiogenic therapy in advanced stages of the disease.

LADERACH DIEGO; GENTILINI, LUCAS; GIRIBALDI, LAURAS; CARDENAS DELGADO, VICTOR; NUGNES, LORENA; CROCI, DIEGO O; AL NAKOUZI, NADER; SACCA, PAULA; CASAS, GABRIEL; MAZZA, OSVALDO; SHIPP, MARGARET; VAZQUEZ, ELBA; CHAUCHEREAU, ANNE; KUTOK, JEFF; RODIG, SCOTT; ELOLA, MARIA T; RABINOVICH, GABRIEL; COMPAGNO, DANIEL

CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

Lugar: Philadelphia; Año: 2012 vol. 73 p. 86 - 96

0008-5472

Galectins, a family of glycan-binding proteins, can influence tumor progression by modulating interactions among tumor, endothelial, stromal and immune cells. Despite considerable progress in identifying the roles of individual galectins in tumor biology, an integrated portrait of the galectin network in different tumor microenvironments remains obscure. We undertook this study to analyze the ‘galectin signature’ of the human prostate cancer (PCa) microenvironment with the overarching goal of selecting novel molecular targets for prognostic and therapeutic purposes. Examination of androgen-dependent and –independent PCa cells and patients samples representing different stages of the disease, revealed that galectin (Gal)-1 is the most abundantly expressed galectin in PCa tissue and is substantially up-regulated during disease progression. In contrast, all other galectin family members are expressed at lower levels. While Gal-3, -4, -9 and -12 down-regulate their expression during evolution of the disease, Gal-8 does not show any specific regulation profile. Given the prominent role of Gal-1 in PCa evolution and its predominant localization at the tumor-vascular interface, we analyzed the potential role of this ‘proto-type’ lectin during PCa angiogenesis. In human PCa tissue arrays, Gal-1 expression correlated with the blood vessel density, particularly in advanced stages of the disease. Silencing Gal-1 expression in PCa cell lines or in prostate cancer microenvironments reduced tumor vascularization considerably both in vitro and in vivo. Collectively, our findings identify a dynamically regulated ‘galectin-specific signature’, which accompanies disease evolution in PCa, highlighting a major role for Gal-1 as a feasible target of anti-angiogenic therapy in advanced stages of the disease.