2005 Fiscal Year Final Research Report Summary
Enhanced suppression of in vivo tumorigenecity of lung cancer by molecular engineered anti-angiogenic agents
| Project/Area Number |
16590761
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
TAKAHASHI Kazuhisa Juntendo University, Respiratory Medicine, Professor, 医学部, 教授 (80245711)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Kayo Juntendo University, Respiratory Medicine, Assistant, 医学部, 助手 (70365659)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Endostatin / Lung cancer / Integrin receptor / Anti-tumor effect / Recombinant protein / Mice |
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| Research Abstract |
Endostatin (ED) is a carboxyl terminal fragment of collagen XVIII with strong anti-angiogenic activity. ED receptor has been considered specific expression on endothelial cells. Recently, direct anti-tumor effect of ED in colon cancer cells has been reported. Until now, we revealed that a5 integrin is capable of being a functional ED receptor on murine lung cancer cell line, LLC cells. We demonstrated that ED-integrin interaction modulates various in vitro biological functions of LLC cells as we had revealed that immobilized ED helps in LLC cell adhesion and migration in an integrin-dependent manner. We further demonstrated that ED inhibited LLC cell proliferation and induced apoptosis. Furthermore, down regulation of a5 integrin on LLC cells using siRNA technique diminished inhibitory effect of ED on LLC cells. In addition, the binding of ED to a5 integrin on LLC cells induced phosphorylation of focal adhesion kinase (FAK). Moreover, phosphorylation of FAK in LLC cells was inhibited by anti-a5 integrin antibody.
For generation of recombinant ED protein, we have successfully purified full length ED protein using Pichia expression system and demonstrated its inhibitory effect for human umbilical vein endothelial cells (HUVEC). Subsequently, we are engineering and generating recombinant ED proteins corresponding to several ED domains
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