Expression of matrix metalloproteinases and related tissue inhibitors in the cyst fluids of ovarian mucinous neoplasms.
OBJECTIVE
The growth of an ovarian cystic neoplasm often involves its invasion into and destruction of the extracellular matrix. We examined neoplastic cysts of ovarian mucinous tumors for the presence of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) using zymography (in situ zymography, gelatin zymography, and casein zymography) and enzyme-linked immunosorbent assay.


RESULTS
Matriolytic activity was detected within the cystic contents and cytoplasm of the lining epithelial cells of the cyst by in situ zymography. This intracystic matriolytic activity was thought to originate mainly in the epithelial cells. The activated form of MMP-9 was seen in all carcinoma and borderline fluids and in 7 of 15 adenomas. The concentration of MMP-9 was higher in carcinoma fluids than in borderline and adenoma fluids (P < 0.05). TIMP-1, which specifically binds to MMP-9, was also higher in carcinoma and borderline fluids than in adenoma fluids (P < 0.05). MMP-2 activity was nearly ubiquitously present in all cyst fluids, irrespective of the fluid's histologic category. The amount of MMP-2 was highest in the carcinoma category, although not to a statistically significant degree. TIMP-2, a specific inhibitor for MMP-2, was significantly lower in the borderline category than in the adenoma category. The molar ratios of TIMP-1/MMP-9 (not significant) and TIMP-2/MMP-2 (P < 0.05) were higher in the adenoma category. Expressions of trypsin, MMP-7, and MMP-9 were generally higher in carcinoma and borderline fluids than in adenoma fluids.


CONCLUSIONS
These observations indicate the importance of ovarian cystic fluids for analyzing tumor-associated matriolytic activities. The findings suggest that these matriolytic enzymes, together with the presence of their inhibitors, play an important role in the growth of ovarian mucinous tumors.
Furuya
M
M
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Ishikura
H
H
Kawarada
Y
Y
Ogawa
Y
Y
Sakuragi
N
N
Fujimoto
S
S
Yoshiki
T
T
D002288:Adenocarcinoma, Mucinous / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020420:Cyst Fluid / Q000201:enzymology* / Q000378:metabolism; D018282:Cystadenocarcinoma, Mucinous / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018291:Cystadenoma, Mucinous / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D005780:Gelatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9