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

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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 and Affiliations

  1. Department of Pediatrics, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York, 11040, USA

    Mingsheng Wang, Yiliang E Liu & Y Eric Shi

  2. Department of Pathology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York, 11040, USA

    Alexander Fuchs & Y Eric Shi

  3. Department of Radiation Oncology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York, 11040, USA

    Eliot M Rosen

  4. Division of Cancer Genetics, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binnry Street, Boston, 02115, Massachusetts, USA

    Shijie Sheng

  5. Human Genome Sciences, Inc., Rockville, 20850-3338, Maryland, USA

    John Greene

Authors
  1. Mingsheng Wang
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  2. Yiliang E Liu
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  3. John Greene
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  4. Shijie Sheng
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  5. Alexander Fuchs
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  6. Eliot M Rosen
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  7. Y Eric Shi
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Wang, M., Liu, Y., Greene, J. et al. Inhibition of tumor growth and metastasis of human breast cancer cells transfected with tissue inhibitor of metalloproteinase 4. Oncogene 14, 2767–2774 (1997). https://doi.org/10.1038/sj.onc.1201245

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  • DOI: https://doi.org/10.1038/sj.onc.1201245

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