PMID- 12704667
OWN - NLM
STAT- MEDLINE
DCOM- 20030616
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 105
IP  - 3
DP  - 2003 Jun 20
TI  - Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits tumor growth and 
      angiogenesis in the TIMP-1 transgenic mouse model.
PG  - 340-6
AB  - 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.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Ikenaka, Yasuhide
AU  - Ikenaka Y
AD  - Third Department of Internal Medicine, Nara Medical University, Nara, Japan.
FAU - Yoshiji, Hitoshi
AU  - Yoshiji H
FAU - Kuriyama, Shigeki
AU  - Kuriyama S
FAU - Yoshii, Junichi
AU  - Yoshii J
FAU - Noguchi, Ryuichi
AU  - Noguchi R
FAU - Tsujinoue, Hirohisa
AU  - Tsujinoue H
FAU - Yanase, Koji
AU  - Yanase K
FAU - Namisaki, Tadashi
AU  - Namisaki T
FAU - Imazu, Hiroo
AU  - Imazu H
FAU - Masaki, Tsutomu
AU  - Masaki T
FAU - Fukui, Hiroshi
AU  - Fukui H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Carcinoma, Ehrlich Tumor/metabolism
MH  - Cell Division
MH  - Humans
MH  - Immunohistochemistry
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neoplasm Transplantation
MH  - *Neovascularization, Pathologic
MH  - Promoter Regions, Genetic
MH  - Time Factors
MH  - Tissue Inhibitor of Metalloproteinase-1/*metabolism/*physiology
EDAT- 2003/04/22 05:00
MHDA- 2003/06/17 05:00
CRDT- 2003/04/22 05:00
PHST- 2003/04/22 05:00 [pubmed]
PHST- 2003/06/17 05:00 [medline]
PHST- 2003/04/22 05:00 [entrez]
AID - 10.1002/ijc.11094 [doi]
PST - ppublish
SO  - Int J Cancer. 2003 Jun 20;105(3):340-6. doi: 10.1002/ijc.11094.