Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Proc. Natl. Acad. Sci. USA 2006 103: 15975-80¹

Speaker: 鄭自勝                                  Time: 2007/03/21 14:00~15:00

Commentator: 凌斌 老師                    Place: Room 601

Abstract:

Angiogenesis is essential for the development of tumors and is an important target for tumor diagnosis and therapy. Endothelial cells (EC) are particularly suitable target cells for angiogenesis therapeutic targets, because they are accessible to agents delivered by the blood. Previously, the authors have designed the specific peptide anginex, which is a cytokine-like peptide with potent anti-angiogenic activity against activated endothelial cells². Before this study, the authors, by using yeast two-hybrid system, discovered that galectin-1 (gal-1) is the receptor of anginex. Gal-1 is a member of the β-galactoside–binding protein family, and is involved in various biological functions, such as cells proliferation, apoptosis, adhesion, and migration³. In this study, the authors investigated the role of gal-1 in EC function or vascular biology. First, the authors found that anginex in the vesicular of EC through receptor-mediated uptake, and discovered that gal-1 is overexpressed in tumor EC by immunohistochemistry. Furthermore, the authors determined the role of gal-1 in EC proliferation by treatment of activated EC with gal-1 specific antisense oligodeoxynucleotide (ODN) or antibody. Second, the authors used theTg(fli1:egfp)y1 zebrafish embryo model. There are three prototype galectins in zebrafish (Lgals1-L1, -L2, -L3), and Lgals-L1, -L2 are expressed in embryo. Morpholino-modified antisense oligonucleotides (MOs) were designed to specifically target Lgals-L1, -L2 to further insight in the role of gal-1 during angiogenesis in vivo. Finally, gal-1-wild-type and -null mice were injected with murine F9 teratocarcinoma cells to compare tumor growth in the presence or absence of gal-1. The authors found that tumor progression in gal-1-null mice was impared largely, which resulted from decreased angiogenesis. The authors demonstrated that gal-1 mediates the angiostatic activity of anginex. Furthermore, gal-1 can serve as a target for angiostatic therapy.

References

1. Thijssen VL, et al. Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc. Natl. Acad. Sci. USA (2006) 103: 15975-80

2. Dings RP, et al. Anti-tumor activity of the novel angiogenesis inhibitor anginex. Cancer Lett. (2003) 194: 55–66.

3. Liu FT and Rabinovich GA. Galectins as modulators of tumour progression. Nat Rev Cancer. (2005) 5: 29-41.