The recombinant kringle domain of urokinase plasminogen activator inhibits in vivo malignant glioma growth.
In a previous report, the recombinant kringle domain (UK1) of the urokinase type plasminogen activator (uPA) showed antiangiogenic activity. Here, we investigated in vivo antitumor effects of the UK1 of human uPA employing a brain tumor model. The systemic administration of UK1 purified from pichia expression (10 and 50 mg/kg/day intraperitoneally for 25 days) led to suppress the growth of a U87 human glioma xenograft, implanted into the brains of male BALB/cSlc nude mice, by 35% and 80%, respectively. In the immunohistochemical analysis, the tumors treated with UK1 showed decreased vascularity and expression of angiogenesis-related factors including vascular endothelial growth factor (VEGF), angiogenin, alpha-smooth muscle actin, von Willebrand's factor, and CD31 (PECAM-1 [Platelet endothelial cell adhesion molecule-1]), and increased apoptosis. UKl inhibited the in vitro proliferation and tube formation of VEGF-stimulated endothelial cells but not the proliferation of glioma cells. These results suggest that UK1 inhibits the malignant glioma growth by suppression of angiogenesis.
Kim
Chung Kwon
CK
Cancer Research Institute, Catholic University of Korea, Seoul 137-701, Republic of Korea.
Hong
Sung Hee
SH
Joe
Young Ae
YA
Shim
Byoung-Shik
BS
Lee
Suk-Keun
SK
Hong
Yong-Kil
YK
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018082:Kringles; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D011994:Recombinant Proteins; D014568:Urokinase-Type Plasminogen Activator