title: Production of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas.
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.
authors.affiliation: The Second Department of Surgery, Nagoya City University Medical School, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Iwata
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Iwase
authors.forename: A
authors.initials: A
authors.lastname: Masaoka
authors.forename: N
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017364:Collagenases / Q000096:biosynthesis; D046508:Culture Techniques; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D018093:Gelatinases / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011480:Protease Inhibitors / Q000378:metabolism*; D014176:Protein Biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D006023:Glycoproteins; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9