Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits tumor growth and angiogenesis in the TIMP-1 transgenic mouse model
| العنوان: | Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits tumor growth and angiogenesis in the TIMP-1 transgenic mouse model |
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| المؤلفون: | Hiroshi Fukui, Tadashi Namisaki, Junichi Yoshii, Tsutomu Masaki, Hitoshi Yoshiji, Hirohisa Tsujinoue, Koji Yanase, Hiroo Imazu, Ryuichi Noguchi, Shigeki Kuriyama, Yasuhide Ikenaka |
| المصدر: | International Journal of Cancer. 105:340-346 |
| بيانات النشر: | Wiley, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Genetically modified mouse, Cancer Research, medicine.medical_specialty, Time Factors, Angiogenesis, Transgene, Mice, Transgenic, Biology, Matrix metalloproteinase, Neovascularization, Mice, Internal medicine, medicine, Animals, Humans, Carcinoma, Ehrlich Tumor, Promoter Regions, Genetic, Cytotoxicity, Tissue Inhibitor of Metalloproteinase-1, Neovascularization, Pathologic, Cell growth, Immunohistochemistry, In vitro, Mice, Inbred C57BL, Endocrinology, Matrix Metalloproteinase 9, Oncology, Cancer research, Matrix Metalloproteinase 2, medicine.symptom, Cell Division, Neoplasm Transplantation |
| الوصف: | 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. |
| تدمد: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.11094 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4d75b6d2e581389b5610a079a729c40 https://doi.org/10.1002/ijc.11094 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....b4d75b6d2e581389b5610a079a729c40 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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| DOI: | 10.1002/ijc.11094 |