Overexpression of matrix metalloproteinase (MMP)-9 correlates with metastatic potency of spontaneous and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced transplantable osteosarcomas in rats
Overexpression of matrix metalloproteinase (MMP)-9 correlates with metastatic potency of spontaneous and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced transplantable osteosarcomas in rats
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DOI：
10.1016/s0304-3835(98)00368-1
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发表时间：
1999-04-01
期刊：
影响因子：
9.7
通讯作者：
Konishi, Y
中科院分区：
文献类型：
--
作者：
Kido, A;Tsutsumi, M;Konishi, Y
在本实验中，通过Northern印迹分析研究了高转移性和低转移性大鼠可移植性骨肉瘤中基质金属蛋白酶（MMP）-2和MMP-9（MMP家族中的关键蛋白）以及金属蛋白酶组织抑制剂（TIMP）-1和TIMP-2（分别针对MMP-2和MMP-9的拮抗蛋白）的表达。两种可移植性骨肉瘤，一种是由致癌剂4-羟基氨基喹啉1-氧化物（4-HAQO）（COS，化学致癌剂诱导的骨肉瘤）诱导的，另一种是自发性病变（SOS，自发性骨肉瘤），从肺结节反复移植，产生具有高转移能力的细胞系，C-SLM（化学致癌剂诱导的骨肉瘤，选择性肺转移性病变）和S-SLM （自发性骨肉瘤、选定的肺转移病灶）。 MMP-9 在 S-SLM 和 C-SLM 中均过表达，而 TIMP-2 在 S-SLM 中过表达。在两种具有高转移潜力的可移植骨肉瘤中，MMP-2 和 TIMP-1 均未过度表达。通过酶谱研究，活性形式 MMP-9 在 S-SLM 和 C-SLM 中增加，但在 SOS 和 COS 中没有增加。MMP-9 mRNA 表达与活性形式 MMP-9 的明胶分解活性 (r = 0.85，P < 0.0001) 和 MMP-9 的活化比率高度相关 (r = 0.83，P < 0.0001)。然而，并非在所有情况下都检测到活性形式 MMP-2。这些结果表明MMP-9 mRNA的过度表达是大鼠可移植性骨肉瘤获得转移潜力的重要因素之一。 (C) 1999 年由爱思唯尔科学有限公司出版。保留所有权利。
In the present experiment, the expression of matrix metalloproteinase (MMP)-2 and MMP-9, key proteins in the MMP family, and the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, antagonistic proteins against MMP-2 and MMP-9, respectively, were investigated by Northern blot analysis in rat transplantable osteosarcomas with high and low metastatic potencies. Two transplantable osteosarcomas, one induced with the carcinogen, 4-hydroxyaminoquinoline 1-oxide (4-HAQO) (COS, chemical carcinogen-induced osteosarcoma), and the other, a spontaneous lesion (SOS, spontaneous osteosarcoma), were repeatedly transplanted from lung nodules to generate lines with high metastatic potency, C-SLM (chemical carcinogen-induced osteosarcoma, selected lung metastatic lesions) and S-SLM (spontaneous osteosarcoma, selected lung metastatic lesions), respectively. MMP-9 was overexpressed in both S-SLM and C-SLM, and TIMP-2 in the case of S-SLM. Neither MMP-2 nor TIMP-1 was overexpressed in either of the transplantable osteosarcomas with high metastatic potentials. The active form MMP-9, studied by zymography, increased in S-SLM and C-SLM but not in SOS and COS. MMP-9 mRNA expression was highly correlated with the gelatinolytic activity of active form MMP-9 (r = 0.85, P < 0.0001) and with the activation ratio of MMP-9 (r = 0.83, P < 0.0001). However, the active form MMP-2 was not detectable in all cases. These results suggest that overexpression of MMP-9 mRNA is one of the essential factors in the acquisition of metastatic potential in rat transplantable osteosarcomas. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.