Activation of matrix metalloproteinase-2 in head and neck squamous cell carcinoma: Studies of clinical samples and in vitro cell lines co-cultured with fibroblasts

Yutaka Tokumaru, Masato Fujii, Yoshihide Otani, Kaori Kameyama, Yorihisa Imanishi, Naoki Igarashi, Jin Kanzaki

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We undertook this present study to investigate the activation of matrix metalloproteinase-2 (MMP-2) in human head and neck squamous cell carcinomas (HNSCC) tissues and cell lines. Gelatinolytic activities of active MMP-2 were significantly higher in carcinoma samples than in normal portions. Furthermore, the activation ratio of proMMP-2 significantly correlated with cervical lymph node metastasis. In vitro studies revealed an HNSCC cell line, HEp-2, to produce neither the pro form nor the active form of MMP-2, but human fibroblasts were found to produce proMMP-2. However, coculture of HEp-2 cells with fibroblasts resulted in the production of not only proMMP-2 but also activeMMP-2 in the culture medium. Northern blot analysis revealed a stronger expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), which is a specific activator of MMP-2, mRNA in HEp-2 cells than in fibroblasts. These results suggest the activation of proMMP-2 as an important event in the process of HNSCC metastasis. They also suggest MMP-2 is secreted in its pro form by stromal fibroblasts surrounding the cancer cells and activated by MT1-MMP localized on the cancer cells. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)15-21
Number of pages7
JournalCancer Letters
Issue number1
Publication statusPublished - 2000 Mar 13



  • Fibroblast
  • Head and neck carcinoma
  • Matrix metalloproteinase-2
  • Membrane-type 1 matrix metalloproteinase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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