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
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)