Reference - Detail
| RRC ID | 41854 |
|---|---|
| Author | Ikenaka Y, Yoshiji H, Kuriyama S, Yoshii J, Noguchi R, Tsujinoue H, Yanase K, Namisaki T, Imazu H, Masaki T, Fukui H. |
| Title | Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits tumor growth and angiogenesis in the TIMP-1 transgenic mouse model. |
| Journal | 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. |
| Volume | 105(3) |
| Pages | 340-6 |
| Published | 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 |
| Times Cited | 81 |
| WOS Category | ONCOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 6 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Ehrlich(RCB0142) |