Kikkawa F, Tamakoshi K, Nawa A, Shibata K, Yamagata S, Yamagata T, Suganuma N
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Cancer Lett. 1997 Nov 25;120(1):109-15. doi: 10.1016/s0304-3835(97)00295-4.
To investigate the relation between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in malignant ovarian tumor, MMP and TIMP activities in conditioned media of 16 malignant ovarian tumor tissues and six normal ovaries were detected by zymography and reverse zymography, respectively and were quantitated with a densitometer. TIMP-1 and TIMP-2 were detected in all normal and malignant ovarian tumor tissues by reverse zymography. In normal ovaries, the intensity of TIMP-2 bands was stronger than TIMP-1, but in malignant tumor tissues those of TIMP-1 were stronger. The ratios of TIMP-1 to TIMP-2 and MMP-9 to MMP-2 were significantly higher in malignant tumor tissues than in normal ovaries (P < 0.001). TIMP activity consisting of TIMP-1 and TIMP-2 correlated significantly to MMP activity of MMP-2 and MMP-9 (r = 0.67, P < 0.005). There was a significant correlation between TIMP-1 activity and MMP activity (r = 0.72, P < 0.001), but no correlation was observed between TIMP-2 activity and MMP activity. The high level of TIMP-1 appeared to be related to malignant phenotype in ovaries as well as the high level of MMP-9.
为研究基质金属蛋白酶(MMP)与金属蛋白酶组织抑制剂(TIMP)在恶性卵巢肿瘤中的关系,分别采用酶谱法和反向酶谱法检测了16例恶性卵巢肿瘤组织和6例正常卵巢组织条件培养基中的MMP和TIMP活性,并用密度计进行定量分析。通过反向酶谱法在所有正常和恶性卵巢肿瘤组织中均检测到了TIMP-1和TIMP-2。在正常卵巢中,TIMP-2条带的强度强于TIMP-1,但在恶性肿瘤组织中TIMP-1的条带强度更强。恶性肿瘤组织中TIMP-1与TIMP-2以及MMP-9与MMP-2的比值显著高于正常卵巢(P < 0.001)。由TIMP-1和TIMP-2组成的TIMP活性与MMP-2和MMP-9的MMP活性显著相关(r = 0.67,P < 0.005)。TIMP-1活性与MMP活性之间存在显著相关性(r = 0.72,P < 0.001),但未观察到TIMP-2活性与MMP活性之间存在相关性。高水平的TIMP-1似乎与卵巢中的恶性表型以及高水平的MMP-9有关。