Production of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas
Production of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas
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DOI：
10.1111/j.1349-7006.1996.tb00266.x
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发表时间：
1996-06-01
期刊：
影响因子：
--
通讯作者：
Okada, Y
中科院分区：
文献类型：
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作者：
Iwata, H;Kobayashi, S;Okada, Y
我们检测了基质金属蛋白酶(MMP)-1（组织胶原酶）、MMP-2（明胶酶A）、MMP-3（基质溶素-1）、MMP-9（明胶酶B）、金属蛋白酶(TIMP)-1和TIMP-2组织抑制剂在人乳腺癌中的产生和组织定位。在半数以上的病例中，MMP-1、MMP-2、MMP-9、TIMP-1和TIMP-2免疫定位于癌细胞中，MMP-2也出现在癌细胞膜上，而MMP-3阳性染色的病例不到15%，scrous癌细胞中MMP-1的染色明显高于其他类型的癌细胞。MMP-9在有淋巴结转移的肿瘤中的表达明显高于无淋巴结转移的肿瘤。MMP-3主要表达于肿瘤基质浸润的t淋巴细胞中。除MMP-3外，基质成纤维细胞均呈阳性。癌组织释放到培养基中的TIMP-1水平明显低于纤维腺瘤组织，但MMP-1、MMP-2、MMP-9和TIMP-2水平差异无统计学意义。明胶酶谱分析显示MMP-2酶原（proMMP-2）的激活率在淋巴结转移的晚期癌组明显高于转移阴性和纤维腺瘤组。这些数据表明MMP-1、MMP-2和MMP-9在人乳腺癌组织中高表达，提示proMMP-2的激活可能是乳腺癌淋巴结转移的一个指标。
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.