Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

Angiostatic activity of human plasminogen fragments is highly dependent on glycosylation

2009; Wiley; Volume: 101; Issue: 2 Linguagem: Inglês

10.1111/j.1349-7006.2009.01403.x

1349-7006

Ivan Carlos dos Santos, Vivian Nogueira Silbiger, Débora Ayame Higuchi, Maria Aparecida Gomes, Lucíola S. Barcelos, Mauro Martins Teixeira, Míriam Teresa Paz Lopes, Valbert Nascimento Cardoso, Mercia Paula Lima, Ronaldo C. Araújo, João Bosco Pesquero, Jorge L. Pesquero,

Glycosylation and Glycoproteins Research

To assess the importance of carbohydrate moieties to the anti‐angiogenic activity of plasminogen fragments, we cloned the fragment corresponding to amino acids Val 79 to Thr 346 (Kint3–4) that presents the three glycosylation sites. The activity of glycosylated and unglycosylated Kint3–4 was tested in murine sponge implant model. We observed a significant decrease in the neovascularization on the sponge after treatment with Kint3–4 by histological examination and determination of the hemoglobin levels. The effects were more intense with the glycosylated than the unglycosylated protein. 99m Technecium‐labeled red blood cells confirmed the inhibition of cell infiltration in the implanted sponge. Studies using melanoma B16F1 implanted in a mouse demonstrated that treatment with glycosylated Kint3–4 (0.15 nmol/48 h) during 14 days suppresses tumor growth by 80%. The vascular endothelial growth factor mRNA levels on the tumor were reduced after treatment. Kint3–4 is a potent plasminogen fragment that has been found to inhibit tumor growth. ( Cancer Sci 2009)