Preparation and characterization of RGD tumour-homing-peptide-modified plasminogen K5.
Plasminogen K5 (kringle 5) has strong inhibitory effects on endothelial-cell proliferation and migration. It was reported that K5 can reduce tumour neovascularization, resulting in clinically relevant antitumour effects. To determine whether addition of a tumour-targeting peptide could improve the tumour homing and antitumour activities of K5, we genetically modified K5 with an RGD (Arg-Gly-Asp) motif, which is a ligand with high affinity for αvβ₃ and αvβ₅ integrins. The fusion protein RGD-K5 was expressed in the Pichia pastoris system and the biological activity of RGD-K5 was assessed in vitro and in vivo. The results showed that the RGD-K5 exhibited a more potent effect of inhibiting endothelial cell proliferation and migration compared with that of traditional K5. RGD-K5 also displayed stronger anti-angiogenic activity in a CAM (chick chorioallantoic membrane) assay. Furthermore, RGD-K5 also showed stronger anti-angiogenic and antitumour effects in B16F10 melanoma-bearing mice compared with traditional K5. In conclusion, the biological activity of K5 can be further improved by the addition of a tumour-homing peptide, and the RGD-K5 may prove to be a promising novel candidate for cancer therapy.
Wang
Yang
Y
Department of Basic Medical Science, Medical College of Xiamen University, 168 Daxue Road, Xiamen, 361005, People's Republic of China.
Guo
Zhongqiang
Z
Ge
Qing
Q
Wang
Enhua
E
Zhang
Xiuli
X
Jin
Guanghui
G
D000818:Animals; D000906:Antibodies / Q000302:isolation & purification; D019496:Cancer Vaccines / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D003001:Cloning, Molecular; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009842:Oligopeptides / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D010843:Pichia / Q000235:genetics; D010958:Plasminogen / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D019496:Cancer Vaccines; D009842:Oligopeptides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C491499:plasminogen kringle 5; C047981:arginyl-glycyl-aspartic acid; D010958:Plasminogen