NGR enhanced the anti-angiogenic activity of tum-5.
Tumstatin is an angiogenesis inhibitor. The anti-angiogenic activity of tumstatin is localized to the 54-132 amino acids. NGR motif is a marker of angiogenic endothelial cells. We synthesized the gene fragment encoding the amino acids 45-132 of tumstatin (tum-5) and coupled a NGR (CNGRCVSGCAGRC) motif to the C-terminal of tum-5 (tum-5-NGR). The both were inserted into pQE30 expression vector and expressed in Escherichia coli. The anti-angiogenic effects of tum-5-NGR and tum-5 were examined in vivo. The results demonstrated the effect of the former was more significant than the latter. After S180 murine cancer xenografts in BALB/c mice were treated with tum-5-NGR or tum-5, tum-5-NGR displayed more significant tumor growth inhibition than tum-5. Binding of tum-5-NGR to normal and tumor tissues was also evaluated. The results showed that the accumulation of tum-5-NGR in tumor tissue was much more than in normal tissues. These data suggest that NGR enhance the anti-angiogenic activity of tum-5.
Meng
Jieru
J
Biotechnology Center of The Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, People's Republic of China.
Ma
Nan
N
Yan
Zhen
Z
Han
Wei
W
Zhang
Yingqi
Y
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001324:Autoantigens / Q000737:chemistry* / Q000627:therapeutic use*; D024141:Collagen Type IV / Q000737:chemistry* / Q000627:therapeutic use*; D015870:Gene Expression; D051379:Mice; D008807:Mice, Inbred BALB C; D011487:Protein Conformation; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000627:therapeutic use*; D012510:Sarcoma 180 / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001324:Autoantigens; D024141:Collagen Type IV; D011993:Recombinant Fusion Proteins; C057112:type IV collagen alpha3 chain