In vitro modulation of MMP-2 and MMP-9 in adult human sarcoma cell lines by cytokines, inducers and inhibitors.
In vitro modulation of MMP-2 and MMP-9 in adult human sarcoma cell lines by cytokines, inducers and inhibitors.
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DOI：
10.3892/ijo.2013.2113
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发表时间：
2013-12
影响因子：
5.2
通讯作者：
Niedzwiecki A
中科院分区：
文献类型：
--
作者：
Roomi MW;Kalinovsky T;Monterrey J;Rath M;Niedzwiecki A
高度侵袭性的成人肉瘤以高水平的基质金属蛋白酶-2和-9为特征，它们通过降解细胞外膜导致癌细胞向远端器官扩散，在肿瘤的侵袭和转移中发挥关键作用。我们研究了细胞因子、有丝分裂原、诱导剂和抑制物对软骨肉瘤(SW-1353)、纤维肉瘤(HT-1080)、脂肪肉瘤(SW-872)和滑膜肉瘤(SW-982)细胞分泌基质金属蛋白酶-2和基质金属蛋白酶-9的影响。选定的化合物包括天然细胞因子和生长因子，以及用于治疗肉瘤的化合物和具有抗癌治疗潜力的天然化合物。用明胶酶谱分析受试剂作用24 h后分泌的基质金属蛋白酶-2和基质金属蛋白酶-9，并用密度法进行定量。纤维肉瘤、软骨肉瘤、脂肪肉瘤和滑膜肉瘤均显示出与基质金属蛋白酶-2和基质金属蛋白酶-9相对应的条带，佛波酯(PMA)对基质金属蛋白酶-9的表达呈剂量依赖性增强。在软骨肉瘤细胞中，肿瘤坏死因子-α对基质金属蛋白酶-9有刺激作用，而对基质金属蛋白酶-2和白细胞介素1β刺激的基质金属蛋白酶-9和基质金属蛋白酶-2的作用不明显。在纤维肉瘤和脂肪肉瘤细胞中，肿瘤坏死因子-α对基质金属蛋白酶-9有明显的刺激作用，但对基质金属蛋白酶-2无明显作用；滑膜肉瘤对基质金属蛋白酶-2有抑制作用，对基质金属蛋白酶-9无影响。IL-1β对纤维肉瘤、脂肪肉瘤和滑膜肉瘤的抑制作用较弱，对滑膜肉瘤的抑制作用较弱，而对滑膜肉瘤的抑制作用较弱。脂多糖在纤维肉瘤和软骨肉瘤中促进基质金属蛋白酶-2的表达，而在脂肪肉瘤中抑制基质金属蛋白酶-2的表达。多西环素、表没食子儿茶素没食子酸酯和营养混合物对所有细胞系的基质金属蛋白酶-2和基质金属蛋白酶-9均有抑制作用。放线菌素-D、环己胺、维甲酸和地塞米松对软骨肉瘤和纤维肉瘤细胞中的基质金属蛋白酶-2和-9有抑制作用。我们的结果表明，细胞因子、有丝分裂原、诱导剂和抑制物对成人肉瘤细胞系中基质金属蛋白酶-2和基质金属蛋白酶-9的表达有上调或下调作用，提示这些药物可能是治疗这些肿瘤的有效策略。
The highly aggressive adult sarcomas are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9, which play crucial roles in tumor invasion and metastasis by degradation of the extracellular membrane leading to cancer cell spread to distal organs. We examined the effect of cytokines, mitogens, inducers and inhibitors on MMP-2 and MMP-9 secretion in chondrosarcoma (SW-1353), fibrosarcoma (HT-1080), liposarcoma (SW-872) and synovial sarcoma (SW-982) cell lines. The selected compounds included natural cytokines and growth factors, as well as chemical compounds applied in therapy of sarcoma and natural compounds that have demonstrated anticancer therapeutic potential. MMP-2 and MMP-9 secretions were analyzed by gelatinase zymography following 24-h exposure to the tested agents and quantitated by densitometry. Fibrosarcoma, chondrosarcoma, liposarcoma and synovial sarcoma showed bands corresponding to MMP-2 and MMP-9 with dose-dependent enhancement of MMP-9 with phorbol 12-myristate 13-acetate (PMA) treatment. In chondrosarcoma cells, tumor necrosis factor (TNF)-α had a stimulatory effect on MMP-9 and insignificant effect on MMP-2 and interleukin (IL)-1β stimulated MMP-9 and MMP-2. In fibrosarcoma and liposarcoma cells, TNF-α had a profound stimulatory effect on MMP-9, but no effect on MMP-2 and in synovial sarcoma an inhibitory effect on MMP-2 and no effect on MMP-9. IL-1β had a slight inhibitory effect on fibrosarcoma, liposarcoma and synovial sarcoma MMP-2 and MMP-9 except for MMP-9 in synovial sarcoma which showed slight stimulation. Lipopolysaccharide (LPS) stimulated expression of MMP-2 in fibrosarcoma and chondrosarcoma while inhibited it in liposarcoma. Doxycycline, epigallocatechin gallate and the nutrient mixture inhibited MMP-2 and MMP-9 in all cell lines. Actinomycin-D, cyclohexamide, retinoic acid, and dexamethasone inhibited MMP-2 and -9 in chondrosarcoma and fibrosarcoma cells. Our results show that cytokines, mitogens, inducers and inhibitors have an up or down regulatory effect on MMP-2 and MMP-9 expression in adult sarcoma cell lines, suggesting these agents may be effective strategies to treat these cancers.
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影响因子：
9.2
作者：
Niedzwiecki, A.;Roomi, M. W.;Kalinovsky, T.;Rath, M.
通讯作者：
Rath, M.
影响因子：
4.2
作者：
Roomi, M. W.;Monterrey, J. C.;Niedzwiecki, A.
通讯作者：
Niedzwiecki, A.
影响因子：
3.6
作者：
Graeven, U;Andre, N;Schmiegel, W
通讯作者：
Schmiegel, W
影响因子：
6.4
作者：
Liu, ZW;Ivanoff, A;Klominek, J
通讯作者：
Klominek, J
DOI：
10.1073/pnas.0506390102
发表时间：
2005-09-20
影响因子：
11.1
作者：
Chen, Q;Espey, MG;Levine, M
通讯作者：
Levine, M