TY - JOUR
T1 - A hybrid protein of the amino-terminal fragment of urokinase and mutant plasminogen activator inhibitor-2 efficiently inhibits tumor cell invasion and metastasis
AU - Wang, Xia
AU - Hou, Min
AU - Tan, Li
AU - Sun, Xinghui
AU - Zhang, Yuqing
AU - Li, Ping
AU - Zhu, Yunsong
N1 - Funding Information:
Acknowledgement The work was supported by a grant from the National Natural Science Foundation of China (No. 30170398).
PY - 2005/2
Y1 - 2005/2
N2 - The urokinase plasminogen activator(uPA) system plays important roles in tumor cell invasion and metastasis. In the present study, we evaluated the effects of ATF-PAI2CD, a hybrid protein of the amino-terminal fragment of urokinase and mutant plasminogen activator inhibitor-2, on 95D cells in vitro and in vivo. Furthermore, our results support a current hypothesis that fusion protein blocks tumor invasion and motility by inhibiting localized pericellular proteolysis. Treatment of 95D cells with ATF-PAI2CD resulted in a dose-dependent decrease in tumor-cell invasion through matrigel, and ATF-PAI2CD was much more effective than PAI-2CD. In addition, extracellular regular protein kinase (ERK1/2) expression was downregulated and the adhesion ability to fibronectin was increased in 95D cells treated with the fusion protein, which was confirmed by cell adhesion assay. A high-concentration of ATF-PAI2CD caused a significant reduction in tumor volume and weight in BALB/c (nu/nu) mice female inoculated with human 95D cells (5×106); the antitumor effects were significant, which demonstrated a 67.9 ± 4.2% reduction in tumor growth compared with control mice. The number of lymphatic metastasis was significantly reduced in mice treated with high- and middle- concentrations of ATF-PAI2CD, whereas a low-concentration of ATF-PAI2CD failed to exhibit any antimetastatic effects. In conclusion, the results suggested that the hybrid protein has therapeutic potential for lung carcinoma and other tumors to inhibit tumor invasion and metastasis.
AB - The urokinase plasminogen activator(uPA) system plays important roles in tumor cell invasion and metastasis. In the present study, we evaluated the effects of ATF-PAI2CD, a hybrid protein of the amino-terminal fragment of urokinase and mutant plasminogen activator inhibitor-2, on 95D cells in vitro and in vivo. Furthermore, our results support a current hypothesis that fusion protein blocks tumor invasion and motility by inhibiting localized pericellular proteolysis. Treatment of 95D cells with ATF-PAI2CD resulted in a dose-dependent decrease in tumor-cell invasion through matrigel, and ATF-PAI2CD was much more effective than PAI-2CD. In addition, extracellular regular protein kinase (ERK1/2) expression was downregulated and the adhesion ability to fibronectin was increased in 95D cells treated with the fusion protein, which was confirmed by cell adhesion assay. A high-concentration of ATF-PAI2CD caused a significant reduction in tumor volume and weight in BALB/c (nu/nu) mice female inoculated with human 95D cells (5×106); the antitumor effects were significant, which demonstrated a 67.9 ± 4.2% reduction in tumor growth compared with control mice. The number of lymphatic metastasis was significantly reduced in mice treated with high- and middle- concentrations of ATF-PAI2CD, whereas a low-concentration of ATF-PAI2CD failed to exhibit any antimetastatic effects. In conclusion, the results suggested that the hybrid protein has therapeutic potential for lung carcinoma and other tumors to inhibit tumor invasion and metastasis.
KW - Hybrid protein
KW - Tumor cell invasion
KW - Urokinase plasminogen activator
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U2 - 10.1007/s00432-004-0623-2
DO - 10.1007/s00432-004-0623-2
M3 - Article
C2 - 15490235
AN - SCOPUS:13244256811
SN - 0171-5216
VL - 131
SP - 129
EP - 136
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
IS - 2
ER -