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Inhibition of tumor growth and metastasis of human breast cancer cells transfected with tissue inhibitor of metalloproteinase 4.

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.
AuthorsM Wang, Y E Liu, J Greene, S Sheng, A Fuchs, E M Rosen, Y E Shi
JournalOncogene (Oncogene) Vol. 14 Issue 23 Pg. 2767-74 (Jun 12 1997) ISSN: 0950-9232 [Print] England
PMID9190892 (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.)
Chemical References
  • Enzyme Inhibitors
  • Proteins
  • Tissue Inhibitor of Metalloproteinases
  • tissue inhibitor of metalloproteinase-4
  • Metalloendopeptidases
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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