Production of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas

Jpn J Cancer Res. 1996 Jun;87(6):602-11. doi: 10.1111/j.1349-7006.1996.tb00266.x.


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.

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Collagenases / biosynthesis
  • Culture Techniques
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Gelatinases / biosynthesis
  • Glycoproteins / biosynthesis*
  • Humans
  • Immunoenzyme Techniques
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / biosynthesis*
  • Protease Inhibitors / metabolism*
  • Protein Biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-2
  • Tissue Inhibitor of Metalloproteinases


  • Glycoproteins
  • Protease Inhibitors
  • Tissue Inhibitor of Metalloproteinases
  • Tissue Inhibitor of Metalloproteinase-2
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9