title: Angiostatic activity of human plasminogen fragments is highly dependent on glycosylation.
abstract: 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.
authors: Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Ivan Carlos
authors: IC
authors: Santos
authors: Vivian Nogueira
authors: VN
authors: Silbiger
authors: Débora Ayame
authors: DA
authors: Higuchi
authors: Maria Aparecida
authors: MA
authors: Gomes
authors: Lucíola Silva
authors: LS
authors: Barcelos
authors: Mauro Martins
authors: MM
authors: Teixeira
authors: Mirian Teresa Paz
authors: MT
authors: Lopes
authors: Valbert Nascimento
authors: VN
authors: Cardoso
authors: Mercia Paula
authors: MP
authors: Lima
authors: Ronaldo Carvalho
authors: RC
authors: Araujo
authors: João Bosco
authors: JB
authors: Pesquero
authors: Jorge Luiz
authors: JL
authors: Pesquero
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D006031:Glycosylation; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D010958:Plasminogen / Q000737:chemistry / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D039302:Integrin alphaVbeta3; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D010958:Plasminogen