## Abstract Astrocytes are intimately involved in the mechanisms of neural injury and repair. They participate in a variety of homeostatic functions and elicit repair responses as balance mechanisms. Currently, there is a growing appreciation of a more active role of astrocytes in neuronal signalin
Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits tumor growth and angiogenesis in the TIMP-1 transgenic mouse model
✍ Scribed by Yasuhide Ikenaka; Hitoshi Yoshiji; Shigeki Kuriyama; Junichi Yoshii; Ryuichi Noguchi; Hirohisa Tsujinoue; Koji Yanase; Tadashi Namisaki; Hiroo Imazu; Tsutomu Masaki; Hiroshi Fukui
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- French
- Weight
- 224 KB
- Volume
- 105
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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. © 2003 Wiley‐Liss, Inc.
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