Abstract |
We recently identified, cloned, and characterized a novel human tissue inhibitor of metalloproteinases-4, TIMP-4 (Greene et al., 1996). To determine if TIMP-4 can modulate the in vivo growth of human breast cancers, we transfected a full-length TIMP-4 cDNA into MDA-MB-435 human breast cancer cells and studied the orthotopic growth of TIMP-4-transfected (TIMP4-435) versus control (neo-435) clones in the mammary fat pad of athymic nude mice. TIMP4-435 clones expressed TIMP-4 mRNA and produced anti- metalloproteinase ( MMP) activity, while neo-435 clones did not express TIMP-4 mRNA or produce detectable anti- MMP activity. Overexpression of TIMP-4 inhibited the invasion potential of the cells in the in vitro invasion assay. When injected orthotopically into nude mice, TIMP-4 transfectants were significantly inhibited in tumor growth by 4-10-fold in primary tumor volumes; and in an axillary lymph node and lung metastasis as compared with controls. These results suggest the therapeutic potential of TIMP-4 in treating cancer malignant progression.
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Authors | M Wang, Y E Liu, J Greene, S Sheng, A Fuchs, E M Rosen, Y E Shi |
Journal | Oncogene
(Oncogene)
Vol. 14
Issue 23
Pg. 2767-74
(Jun 12 1997)
ISSN: 0950-9232 [Print] England |
PMID | 9190892
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Enzyme Inhibitors
- Proteins
- Tissue Inhibitor of Metalloproteinases
- tissue inhibitor of metalloproteinase-4
- Metalloendopeptidases
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Topics |
- Animals
- Breast Neoplasms
(genetics, pathology)
- Cloning, Molecular
- Enzyme Inhibitors
(pharmacology)
- Female
- Humans
- Metalloendopeptidases
(antagonists & inhibitors)
- Mice
- Mice, Nude
- Molecular Sequence Data
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Proteins
(genetics, pharmacology)
- Tissue Inhibitor of Metalloproteinases
- Transfection
- Tumor Cells, Cultured
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