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. 1996 Jun;87(6):602–611. doi: 10.1111/j.1349-7006.1996.tb00266.x

Production of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Human Breast Carcinomas

Hiroji Iwata 1,✉, Shunzo Kobayashi 1, Hirotaka Iwase 1, Akira Masaoka 1, Noboru Fujimoto 2, Yasunori Okada 3
PMCID: PMC5921148  PMID: 8766524

Abstract

We examined production and tissue localization of matrix metalloproteinase (MMP)‐1 (tissue collagenase), MMP‐2 (gelatinase A), MMP‐3 (stromelysin‐1), MMP‐9 (gelatinase B), tissue inhibitors of metalloproteinase (TIMP)‐1 and TIMP‐2 in human breast carcinomas. In more than half of the cases, MMP‐1, MMP‐2, MMP‐9, TIMP‐1 and TIMP‐2 were immunolocalized in carcinoma cells and MMP‐2 was on the carcinoma cell membranes as well, whereas MMP‐3 was positively stained in less than 15% of the cases. MMP‐1 staining in carcinoma cells was significantly higher in scirrhous carcinoma than in other types of carcinoma. MMP‐9 expression was remarkably higher in the carcinoma cases with lymphnode metastasis than in the non‐metastatic cases. MMP‐3 was mainly expressed in T‐lymphocytes infiltrated in the tumor stroma. Stromal fibroblasts were positive for all these MMPs except for MMP‐3. The TIMP‐1 levels released into the culture media by carcinoma tissues were significantly lower than those by fibroadenoma tissues, although there were no significant differences in the levels of MMP‐1, MMP‐2, MMP‐9 and TIMP‐2. Gelatin zymographical analyses showed that the activation rate of the zymogen of MMP‐2 (proMMP‐2) is significantly higher in the more advanced carcinoma group with lymphnode metastasis than in the metastasis‐negative and fibroadenoma groups. These data indicate that MMP‐1, MMP‐2 and MMP‐9 are highly expressed in human breast carcinoma tissue and suggest that activation of proMMP‐2 may be an indicator of lymphnode metastasis of the breast carcinoma.

Keywords: Matrix metalloproteinase, Tissue inhibitor of metalloproteinase, Cancer invasion, Metastasis, Breast cancer

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