A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key target for treatment of advanced disease

LADERACH, DIEGO; GENTILINI, LUCAS D; GIRIBALDI, LAURA; CÁRDENAS DELGADO, VICTOR M.; NUGNES, LORENA; CROCI, DIEGO O.; AL NAKOUZI, N.; SACCA, PAULA; MAZZA, OSVALDO; SHIPP, MARGARET; VAZQUEZ, ELBA; CHAUCHEREAU, ANNE; KUTOK, JEFFERY L; RODIG, SCOTT J.; ELOLA, MARIA T.; COMPAGNO, DANIEL; RABINOVICH, GABRIEL A.

CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

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

0008-5472

Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interactions between 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 is still missing. 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. In examining androgen-responsive and castration-resistant PCa cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in PCa tissue and was markedly upregulated during disease progression. In contrast, all other galectins were expressed at lower levels: Gal-3, -4, -9 and -12 were downregulated during disease evolution, while expression of Gal-8 was unchanged. Given the prominent regulation of Gal-1 during PCa progression and its predominant localization at the tumor-vascular interface, we analyzed the potential role of this endogenous lectin in PC angiogenesis. In human PCa tissue arrays, Gal-1 expression correlated with the presence of blood vessels, particularly in advanced stages of the disease. Silencing Gal-1 in PCa cells reduced tumor vascularization without altering expression of other angiogenesis-related genes. Collectively, our findings identify a dynamically regulated ´galectin-specific signature’ that accompanies disease evolution in PCa, and they highlight a major role for Gal-1 as a tractable target for anti-angiogenic therapy in advanced stages of the disease.