Contribution of galectin-1 to different steps of tumor progression: a key role in tumor-immune escape and angiogenesis

NATALIA RUBINSTEIN, LAURA PALEARI, MARTA TOSCANO, JUAN M. ILARREGUI, GERMÁN BIANCO, STEFANO IACOBELLI, ADRIANA ALBINI, GABRIEL RABINOVICH

Córdoba, Argentina

Congreso; VII Latin American Congress of Immunology; 2005

Latin American Society of Immunology

Contribution of galectin-1 to different steps of tumor progression: a key role in tumor-immune escape and angiogenesis Rubinstein N1, Paleari L2, Toscano M1, Ilarregui J1, Bianco G1, Iacobelli S3, Albini A2 and Rabinovich G1 1Lab. Inmunogenética. Fac. Medicina. UBA 2National Institute for Cancer Research, Genova. 3University D'Annunzio, Chieti   Tumors develop multiple strategies to evade immune response, generate new blood vessels and regulate cell migration, thereby affecting the process of metastasis. Recently, we demonstrated that galectin-1 (Gal-1), an endogenous lectin found in tumor microenvironment, plays a pivotal role in promoting escape from T-cell-dependent immunity. Blockade of immunosuppressive Gal-1 in vivo promotes tumor rejection and stimulates the generation of a tumor-specific T cell response in syngeneic mice, which are then able to resist subsequent challenge with wild-type tumors. To examine the contribution of Gal-1 to another steps of tumor progression we inhibited Gal-1 expression by silencing-gene strategies in tumor cell lines. These cells were used for in vivo and in vitro assays to study the regulation of angiogenesis and metastasis. Targeted inhibition of Gal-1 gene expression inhibited the formation new blood vessels (p<0.05) and significantly reduced tumor cell invasion (p<0.05). Using lactose and synthetic inhibitors (synthetic lactulose amines) we determined the contribution of Gal-1 to these processes. Finally, in vitro treatment of tumor cells with cytostatic agents significantly modulated Gal-1 expression. Our results suggest that Gal-1 is a key regulator of tumor progression, not only by promoting tumor-immune escape, but also by regulating angiogenesis and cell migration