Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay

Yoshio Tsunezuka, Hiroaki Kinoh, Takahisa Takino, Yoh Watanabe, Yasunori Okada, Akira Shinagawa, Hiroshi Sato, Motoharu Seiki

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Abstract

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a member of the recently identified unique membrane-type subgroup in the matrix metalloproteinase (MMP) family. MT1-MMP has proteolytic activity against components in the extracellular matrix and activates progelatinase A (72-kDa type IV procollagenase/proMMP-2) on the cell surface. Because MT1-MMP is frequently expressed in a variety of tumors, we examined its contribution to their metastatic potential. The mouse lung carcinoma cell line Madison 109 was transiently transfected with a MT1-MMP expression plasmid and inoculated into the tail vein of BALB/c mouse. Fate of the transfected cells was monitored by the neo(r) gene in the plasmid using the quantitative PCR method. The survival rate of the parental cells in lung was 0.7% of the inoculated cells. It was increased by 3-fold with the MT1-MMP transfected cells and the number of the lung nodules increased accordingly. Immunostaining of the consecutive tissue sections revealed that lung nodules expressing MT1-MMP were positive for gelatinase A as well, whereas MT1-MMP- negative cells were not stained for gelatinase A at all. Thus, MT1-MMP- expressing cells acquire specific ability to bind exogenous progelatinase A.

Original languageEnglish
Pages (from-to)5678-5683
Number of pages6
JournalCancer Research
Volume56
Issue number24
Publication statusPublished - 1996 Dec 15
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Tsunezuka, Y., Kinoh, H., Takino, T., Watanabe, Y., Okada, Y., Shinagawa, A., Sato, H., & Seiki, M. (1996). Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay. Cancer Research, 56(24), 5678-5683.