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基质金属蛋白酶的表达取决于软骨肉瘤中有丝分裂原激活蛋白激酶的活性。

Expression of MMPs is dependent on the activity of mitogen-activated protein kinase in chondrosarcoma.

作者信息

Yao Min, Wang Xiaomei, Zhao Yufeng, Wang Xiaomeng, Gao Feng

机构信息

Department of Pathology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.

出版信息

Mol Med Rep. 2017 Feb;15(2):915-921. doi: 10.3892/mmr.2016.6077. Epub 2016 Dec 27.

Abstract

Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) serve an important role in chondrosarcoma. The present study investigated whether the expression of MMPs was dependent on the activity of mitogen-activated protein kinase (MAPK) in chondrosarcoma. Surgical pathological specimens were collected to detect MMP-1, MMP-13, TIMP-1, type II collagen and phosphorylated MAPK levels in normal cartilage, enchondroma and chondrosarcoma tissues. The expression of MMP‑1, MMP‑13, TIMP‑1 and type II collagen was investigated utilizing MAPK inhibitors in chondrosarcoma cells. It was noted that the expression levels of MMP‑1, MMP‑13 and TIMP‑1 were increased in chondrosarcoma with the activity of MAPK. After chondrosarcoma cells were pretreated with MAPK inhibitors, the levels of MMP‑1, MMP‑13 and TIMP‑1 were inhibited. Furthermore, MMP‑1 and MMP‑13 are essential in regulating the degradation of type II collagen and decomposing cartilage matrix major. The high expression levels of MMP‑1 and MMP‑13 in chondrosarcoma expedite the invasion by chondrosarcoma cells and their expression can be depressed by MAPK inhibitors.

摘要

基质金属蛋白酶(MMPs)和基质金属蛋白酶组织抑制剂(TIMPs)在软骨肉瘤中发挥重要作用。本研究调查了软骨肉瘤中MMPs的表达是否依赖于丝裂原活化蛋白激酶(MAPK)的活性。收集手术病理标本,以检测正常软骨、内生软骨瘤和软骨肉瘤组织中MMP-1、MMP-13、TIMP-1、II型胶原蛋白和磷酸化MAPK的水平。利用MAPK抑制剂研究软骨肉瘤细胞中MMP-1、MMP-13、TIMP-1和II型胶原蛋白的表达。结果发现,随着MAPK活性增加,软骨肉瘤中MMP-1、MMP-13和TIMP-1的表达水平升高。软骨肉瘤细胞用MAPK抑制剂预处理后,MMP-1、MMP-13和TIMP-1的水平受到抑制。此外,MMP-1和MMP-13在调节II型胶原蛋白的降解和分解软骨基质主要成分方面至关重要。软骨肉瘤中MMP-1和MMP-13的高表达水平加速了软骨肉瘤细胞的侵袭,并且它们的表达可被MAPK抑制剂抑制。

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