Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas

Hirohisa Ueno, Hiroyuki Nakamura, Masaki Inoue, Kazushi Imai, Masakuni Noguchi, Hiroshi Sato, Motoharu Seiki, Yasunori Okada

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Abstract

Activation of the zymogen of matrix metalloproteinase 2 (proMMP-2, progelatinase A) possibly is one of the key steps in invasion and metastasis f various human carcinomas. Three different membrane-type MMPs (MT-MMPs) MT1- , MT2-, and MT3-MMPs are thought to be activators of proMMP-2 in the tissues. MT4-MMP is structurally different from the other three enzymes, and its function as proMMP-2 activator is uncertain. In the present study of human invasive breast carcinomas, we examined a correlation between the expression of MT1-, MT2-, and MT3-MMPs, immunolocalization of MT1- and MT2-MMPs, and proMMP-2 activation. Northern blot analysis demonstrated the predominant expression of MT1-MMP mRNA in carcinoma tissues (20 of 20 cases), whereas MT2-MMP was detected in only 25% of the cases (5 of 20 cases), and no detectable expression of MT3-MMP was observed. The expression levels of MT1- MMP but not MT2-MMP correlated well with the presence of lymph node and distant metastases, clinical stages, and size of tumors. Immunohistochemically, MT1-MMP was localized predominantly in the carcinoma cells in all of the samples (32 of 32 cases). Immunostaining of MT2-MMP in the carcinoma cells was observed in only 38% of the cases (12 of 32 cases). Immunoblot analysis of tumor homogenates confirmed the presence of these MT- MMPs. Activation of proMMP-2 was significantly higher in the carcinoma samples with lymph node or distant metastasis compared to carcinoma without metastasis, normal control, or fibrocystic disease (P < 0.05). An increase in the activation ratio of proMMP-2 correlated directly with the expression of MT1-MMP but not MT2-MMP, as measured by either Northern blot analysis or immunostaining. These results suggest that MT1-MMP may play a hey role in human breast carcinoma invasion and metastasis by being predominantly responsible for activation of proMMP-2.

Original languageEnglish
Pages (from-to)2055-2060
Number of pages6
JournalCancer Research
Volume57
Issue number10
Publication statusPublished - 1997 May 15

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ueno, H., Nakamura, H., Inoue, M., Imai, K., Noguchi, M., Sato, H., Seiki, M., & Okada, Y. (1997). Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas. Cancer Research, 57(10), 2055-2060.