RRC ID 68547
著者 Yagi H, Ueda M, Jinno H, Aiura K, Mikami S, Tada H, Seno M, Yamada H, Kitajima M.
タイトル Anti-tumor effect in an in vivo model by human-derived pancreatic RNase with basic fibroblast growth factor insertional fusion protein through antiangiogenic properties.
ジャーナル Cancer Sci
Abstract It is thought that the export of angiogenic fibroblast growth factors (FGF) from tumors may be involved in the onset of tumor angiogenesis. To create a new active targeting drug that inhibits the tumor angiogenic process without toxicities to normal cells, human basic FGF (h-bFGF) was inserted genetically into the Gly89 position of cross-linked RNase1 (the ribonuclease inhibitor protein [RI] binding site of cross-linked human pancreatic RNase) to prevent stereospecific binding to RI. The resultant insertional-fusion protein (CL-RFN89) was active both as h-bFGF and as RNase1. Furthermore, it acquired an additional ability of evading RI through steric blockade of RI binding caused by the fused h-bFGF domain. In the present study, the effect of the resultant protein, CL-RFN89, on the antitumor response though its antiangiogenic properties was investigated in an in vivo model. Continuous systemic treatment with CL-RFN89 significantly inhibited the growth of human A431 squamous cell carcinomas in vivo. Seven days of treatment with CL-RFN89 resulted in a 58.2% inhibition of tumor growth compared with control mice (P < 0.0001). Furthermore, immunohistochemistry using a rat antimouse CD31 antibody showed that treatment with CL-RFN89 reduced tumor vascularization. These findings identify CL-RFN89 as a potent systemic inhibitor of tumor growth as a result of its antiangiogenic properties. This protein appears to be a new systemic antitumor agent.
巻・号 97(12)
ページ 1315-20
公開日 2006-12-1
DOI 10.1111/j.1349-7006.2006.00336.x
PII CAS336
PMID 17032310
MeSH Angiogenesis Inhibitors / therapeutic use* Animals Female Fibroblast Growth Factor 2 / genetics* Fibroblast Growth Factor 2 / metabolism Humans Immunoenzyme Techniques Mice Mice, Inbred BALB C Neoplasms, Experimental / drug therapy* Neoplasms, Experimental / pathology Neovascularization, Pathologic / prevention & control* Plasmids Recombinant Fusion Proteins / therapeutic use* Ribonuclease, Pancreatic / genetics* Ribonuclease, Pancreatic / metabolism Tumor Cells, Cultured
IF 4.966
リソース情報
ヒト・動物細胞 A431