RRC ID |
42359
|
著者 |
Cui R, Takahashi K, Takahashi F, Tanabe KK, Fukuchi Y.
|
タイトル |
Endostatin gene transfer in murine lung carcinoma cells induces vascular endothelial growth factor secretion resulting in up-regulation of in vivo tumorigenecity.
|
ジャーナル |
Cancer Lett
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Abstract |
Endostatin (ED) is a carboxyl-terminal fragment of type XVIII collagen with a strong anti-angiogenic activity. The purpose of this study is to determine the effect of ED gene transfer into lung cancer cells on in vivo tumor growth in a murine model. The murine lung cancer cell line, Lewis Lung Carcinoma (LLC), was transfected with ED gene to express and secrete ED. After clones were selected to secrete ED, several stable transfectants with ED gene (LLC/ED) and control transfectants (LLC/Mock) were established. In vitro proliferation of these transfectants demonstrated similar growth speed. In contrast to previous reports, in vivo subcutaneous tumorignecity of LCC/ED transfectants was significantly greater than that of LLC/Mock transfectants. Immunohistochemical staining analysis demonstrated that ED gene transfer induced angiogenesis, suggesting coinduction of another gene implicated for neovascularization. As expected, LLC/ED transfectants secreted not only ED but also vascular endothelial growth factor (VEGF) to a much greater degree than LLC/mock transfectants. Interestingly, culture supernatants of LLC/ED cells enhanced in vitro proliferation of human umbilical vein endothelial cells (HUVEC) to a much greater degree than those of LLC/Mock cells. These results indicate that ED gene transfer in murine lung carcinoma cells induces VEGF secretion, resulting in enhancement of in vivo tumorigenecity in the murine model. More attention should be paid for ED gene therapy into lung cancer cells since it may influence other proteins secretion, which upregulates angiogenesis.
|
巻・号 |
232(2)
|
ページ |
262-71
|
公開日 |
2006-2-8
|
DOI |
10.1016/j.canlet.2005.02.045
|
PII |
S0304-3835(05)00240-5
|
PMID |
15876483
|
MeSH |
Animals
Cell Line, Tumor
Cyclohexanes
Endostatins / genetics*
Endothelial Cells / cytology
Gene Transfer, Horizontal*
Lung Neoplasms / metabolism
Lung Neoplasms / pathology*
Male
Mice
Mice, Inbred C57BL
O-(Chloroacetylcarbamoyl)fumagillol
RNA, Messenger / analysis
Sesquiterpenes / therapeutic use
Transfection
Up-Regulation
Vascular Endothelial Growth Factor A / biosynthesis*
Vascular Endothelial Growth Factor A / genetics
|
IF |
7.36
|
引用数 |
11
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
ヒト・動物細胞 |
LLC(RCB0558) |