Characterization of extracellular matrix-degrading proteinase and its inhibitor in gynecologic cancer tissues with clinically different metastatic form.

Abstract

The authors conducted a comparison study of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase-1 (TIMP-1) activities in clinically different metastatic types of ovarian cancer, cervical cancer, and endometrial cancer tissues. Gelatinase activity in culture medium obtained from each cancer tissue was detected by zymography and was quantitated by densitometer. Tissue inhibitor of metalloproteinase-1 activity was measured in culture medium by the human TIMP-1 enzyme immunoassay kit. Six dominant gelatinases were detected in ovarian, cervical, and endometrial cancers: 200-kDa; 130-kDa; 92-kDa (MMP-9); 83-kDa, which is an active form of 92-kDa gelatinase; 72-kDa (MMP-2); and 66-kDa gelatinase, which is an active form of 72-kDa gelatinase. The 92-kDa and 72-kDa gelatinolytic bands were present in all samples. The expression rates of 200-, 130-, and 83-kDa gelatinase in endometrial cancer and cervical cancer tissues were higher than that observed in ovarian cancer tissue. Densitometric analysis showed that the 92-kDa/72-kDa ratio was significantly higher in cervical cancer tissue than in ovarian and endometrial cancer tissues (P < 0.05), and the 66-kDa/72-kDa ratio was significantly higher in endometrial cancer tissue than in ovarian cancer tissue (P < 0.01). Tissue inhibitor of metalloproteinase-1 activity was significantly lower in cervical cancer tissue than in ovarian and endometrial cancer tissues (P < 0.01). These results reflect the difference of metastatic forms and are indicative of the possibility of the strong relationship to MMP activity in the invasion and metastasis of cervical cancer and endometrial cancer, compared with those of ovarian cancer.