| RRC ID |
42940
|
| 著者 |
Cui R, Ohashi R, Takahashi F, Yoshioka M, Tominaga S, Sasaki S, Gu T, Takagi Y, Takahashi K.
|
| タイトル |
Signal transduction mediated by endostatin directly modulates cellular function of lung cancer cells in vitro.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
Endostatin (ED) is a carboxyl-terminal fragment of collagen XVIII with strong antiangiogenic activity. ED has been considered as a highly specific inhibitor of endothelial cell proliferation and migration through interaction with its receptor on the surface of endothelial cells. Recently, direct antitumor effects of ED in colon cancer cells and head and neck squamous cell carcinoma cells has been reported. However, its effect on lung cancer cells has not been clarified. The purpose of the present study was to determine the effect of ED on in vitro lung cancer cell function and to identify its receptor on lung cancer cells. We revealed that alpha5 integrin is capable of being a functional ED receptor among several integrins that are expressed on murine lung cancer (Lewis lung cancer [LLC]) cells. We further demonstrated that the ED-integrin interaction modulates various in vitro biological functions of LLC cells as we revealed that immobilized ED helps in LLC cell adhesion and migration in an integrin-dependent manner. Furthermore, ED inhibited LLC cell proliferation and induced apoptosis. Interestingly, ED did not demonstrate any antiproliferative activity against the other murine lung cancer cell line, KLN205, that lacks alpha5 integrin but binds to immobilized ED through the beta1 integrin. In addition, the binding of ED to alpha5 integrin on LLC cells induced phosphorylation of focal adhesion kinase. Taken together, these results suggest that the interaction between ED and alpha5 integrin may play an important role in lung cancer cell function.
|
| 巻・号 |
98(6)
|
| ページ |
830-7
|
| 公開日 |
2007-6-1
|
| DOI |
10.1111/j.1349-7006.2007.00459.x
|
| PII |
CAS459
|
| PMID |
17419709
|
| MeSH |
Angiogenesis Inhibitors / pharmacology*
Animals
Carcinoma, Lewis Lung / metabolism*
Carcinoma, Lewis Lung / pathology
Cell Adhesion / drug effects
Cell Movement / drug effects
Cell Proliferation / drug effects
Down-Regulation
Endostatins / pharmacology*
Focal Adhesion Protein-Tyrosine Kinases / metabolism*
Integrin alpha5 / metabolism
Mice
Phosphorylation
Signal Transduction / drug effects
|
| IF |
4.966
|
| 引用数 |
12
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
LLC(RCB0558) |
