| RRC ID |
41854
|
| 著者 |
Ikenaka Y, Yoshiji H, Kuriyama S, Yoshii J, Noguchi R, Tsujinoue H, Yanase K, Namisaki T, Imazu H, Masaki T, Fukui H.
|
| タイトル |
Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits tumor growth and angiogenesis in the TIMP-1 transgenic mouse model.
|
| ジャーナル |
Int J Cancer
|
| Abstract |
The tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) has been recognized as a multifunctional protein. The role of TIMPs in cancer remains the subject of conflicting reports with an antitumor activity or a tumor growth stimulation activity by several mechanisms. The aim of our study is to investigate the effect of ectopic TIMP-1 overexpression on the primary transplanted tumor growth. We employed transgenic mice overexpressing the human TIMP-1 (hTIMP-1) in the liver under control of the albumin promoter/enhancer (TIMP-Tg-mice) and producing high serum levels of TIMP-1. We used the transplantable Ehrlich tumor cells in the current study. The allograft study revealed that the tumor growth in the TIMP-Tg-mice was more significantly inhibited than control (Cont) mice by associated suppression of neovascularization in the tumor. The in vitro studies showed that the recombinant TIMP-1 (rTIMP-1) did not affect the proliferation of the endothelial cells (ECs) and tumor cells, suggesting that the tumor suppressive effect of TIMP-1 was not due to cytotoxicity. TIMP-1 significantly inhibited EC tubular formation in vitro. Furthermore, TIMP-1 treatment did not affect the levels of matrix metalloproteinase (MMP)-2 and MMP-9 mRNA in the Ehrlich tumor cells in vitro, although these expressions in the tumor were markedly suppressed in the TIMP-Tg-mice, compared to the Cont-mice at the end of the experiment. These results suggested that the ectopically overexpressed TIMP-1 inhibited the tumor growth by angiogenesis suppression.
|
| 巻・号 |
105(3)
|
| ページ |
340-6
|
| 公開日 |
2003-6-20
|
| DOI |
10.1002/ijc.11094
|
| PMID |
12704667
|
| MeSH |
Animals
Carcinoma, Ehrlich Tumor / metabolism
Cell Division
Humans
Immunohistochemistry
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasm Transplantation
Neovascularization, Pathologic*
Promoter Regions, Genetic
Time Factors
Tissue Inhibitor of Metalloproteinase-1 / metabolism*
Tissue Inhibitor of Metalloproteinase-1 / physiology*
|
| IF |
5.145
|
| 引用数 |
81
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Ehrlich(RCB0142) |
