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 microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. In examining androgen-responsive and castration-resistant prostate cancer cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in prostate cancer 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, whereas expression of Gal-8 was unchanged. Given the prominent regulation of Gal-1 during prostate cancer progression and its predominant localization at the tumor-vascular interface, we analyzed the potential role of this endogenous lectin in prostate cancer angiogenesis. In human prostate cancer tissue arrays, Gal-1 expression correlated with the presence of blood vessels, particularly in advanced stages of the disease. Silencing Gal-1 in prostate cancer 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 prostate cancer, and they highlight a major role for Gal-1 as a tractable target for antiangiogenic therapy in advanced stages of the disease.
Written by:
Laderach DJ, Gentilini LD, Giribaldi L, Delgado VC, Nugnes L, Croci DO, Al Nakouzi N, Sacca P, Casas G, Mazza O, Shipp MA, Vazquez E, Chauchereau A, Kutok JL, Rodig SJ, Elola MT, Compagno D, Rabinovich GA. Are you the author?
Laboratorio de Glicómica Estructural y Funcional, and Apoptosis y Cancer, IQUIBICEN-CONICET, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, "Universidad de Buenos Aires"; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET); Instituto de Química y Fisicoquímica Biológicas (IQUIFIB, CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires; División Anatomía Patológica, Hospital Alemán; División Urología, Hospital Nacional de Clínicas 'José de San Martín', Ciudad de Buenos Aires, Argentina; Institut Gustave Roussy-INSERM U981, Villejuif, France; Dana-Farber Cancer Institute and Harvard Medical School; and Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Reference: Cancer Res. 2013 Jan 1;73(1):86-96.
doi: 10.1158/0008-5472.CAN-12-1260
PubMed Abstract
PMID: 23108139
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