Statin-AE: a novel angiostatin-endostatin fusion protein with enhanced antiangiogenic and antitumor activity.
The combination of angiostatin and endostatin has been shown to have synergistic antiangiogenic and antitumor effects when the genes for these proteins are delivered to tumor cells by retroviral gene transfer. Here we report the construction of a murine angiostatin-endostatin fusion gene (Statin-AE) which shows enhanced antiangiogenic activity on human umbilical vein endothelial cell (HUVEC) tube formation in vitro compared with angiostatin or endostatin alone. Similarly, the fusion gene demonstrates antiangiogenic effects in vivo and antitumor activity in a B16F10 melanoma model when co-delivered by retroviral packaging cell inoculation in mice. The fusion gene demonstrates significantly greater inhibition of tumor growth compared with angiostatin, endostatin or the combination of genes.
Department of Pathology, Stanford University Medical Center, Stanford, California, USA.
F A
FA
Scappaticci
A
A
Contreras
R
R
Smith
L
L
Bonhoure
B
B
Lum
Y
Y
Cao
E G
EG
Engleman
G P
GP
Nolan
D000595:Amino Acid Sequence; D043168:Angiostatins; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000502:physiology*; D043169:Endostatins; D006801:Humans; D008546:Melanoma, Experimental / Q000098:blood supply; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology*; D010958:Plasminogen / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism*
D043169:Endostatins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D043168:Angiostatins; D010958:Plasminogen; D003094:Collagen