CHARACTERIZATION OF EXTRACELLULAR MATRIX-DEGRADING PROTEINASE AND ITSINHIBITOR IN GYNECOLOGIC CANCER TISSUES WITH CLINICALLY DIFFERENT METASTATIC FORM

Background. The authors conducted a comparison study of matrix metallo proteinase (MMP) and tissue inhibitor of metalloproteinase-l (TIMP-1) activities in clinically different metastatic types of ovarian cancer, cervical cancer, and endometrial cancer tissues. Methods. Gelatinase activity in culture medium obtained from each cancer tissue was detect ed by zymography and was quantitated by densitometer. Tissue inhibitor of metalloproteinase-l activity was measured in culture medium by the human TIMP-1 enzyme immunoassay kit. Results. Six dominant gelatinase s 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 g elatinase; 72-kDa (MMP-2); and 66-kDa gelatinase, which is an active f orm of 72-kDa gelatinase. The 92-kDa and 72-kDa gelatinolytic bands we re 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 anal ysis showed that the 92-kDa/72-kDa ratio was significantly higher in c ervical cancer tissue than in ovarian and endometrial cancer tissues ( P < 0.05), and the 66-kDa/72-kDa ratio was significantly higher in end ometrial cancer tissue than in ovarian cancer tissue (P < 0.01). Tissu e inhibitor of metalloproteinase-l activity was significantly lower in cervical cancer tissue than in ovarian and endometrial cancer tissues (P < 0.01). Conclusions. These results reflect the difference of meta static forms and are indicative of the possibility of the strong relat ionship to MMP activity in the invasion and metastasis of cervical can cer and endometrial cancer, compared with those of ovarian cancer.