CXCR4/SDF1 mediate hypoxia induced chondrosarcoma cell invasion through ERK signaling and increased MMP1 expression.
CXCR4/SDF1 mediate hypoxia induced chondrosarcoma cell invasion through ERK signaling and increased MMP1 expression.
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DOI：
10.1186/1476-4598-9-17
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发表时间：
2010-01-26
期刊：
影响因子：
37.3
通讯作者：
Terek RM
中科院分区：
文献类型：
--
作者：
Sun X;Wei L;Chen Q;Terek RM
软骨肉瘤是一种对常规细胞毒化疗无反应的疾病，MMP 1的表达是预后不良的标志。软骨肉瘤中MMP 1表达增加的机制尚不完全清楚。我们的目标是确定可以作为治疗靶点的分子途径。软骨肉瘤在生长过程中变得缺氧，能够引起血管生成反应，并且通常转移到肺部。本研究确定了缺氧，特别是HIF-1a对CXCR 4和MMP 1表达的影响及其在软骨肉瘤细胞侵袭中的作用。与正常关节软骨相比，CXCR 4及其配体SDF 1在原发性软骨肉瘤肿瘤中上调，与正常软骨细胞相比，CXCR 4在软骨肉瘤细胞系JJ中上调。低氧和HIF-1a增加JJ细胞株CXCR 4和MMP 1的表达和软骨肉瘤的体外侵袭。针对HIF-1a或CXCR 4的siRNA、CXCR 4抑制剂AMD 3100以及ERK抑制剂U 0126和ERK siRNA可以抑制缺氧介导的MMP 1表达增加和软骨肉瘤侵袭。低氧诱导CXCR 4和MMP 1表达增加软骨肉瘤细胞侵袭，并由HIF-1a和ERK介导。CXCR 4阻断可以抑制侵袭和MMP 1，这表明CXCR 4/SDF 1信号传导可能是软骨肉瘤的治疗靶点。
Chondrosarcoma is a disease that does not respond to conventional cytotoxic chemotherapy and expression of MMP1 is a marker for a poor prognosis. The mechanism of increased MMP1 expression in chondrosarcoma is not completely known. Our goal is to identify molecular pathways that could serve as therapeutic targets. Chondrosarcoma become hypoxic as they grow, are capable of eliciting an angiogenic response, and typically metastasize to the lungs. The present study determined the effect of hypoxia and specifically HIF-1a on expression of CXCR4 and MMP1 and their role in chondrosarcoma cell invasion. CXCR4 and its ligand, SDF1, are upregulated in primary chondrosarcoma tumors compared to normal articular cartilage, and CXCR4 was upregulated in chondrosarcoma cell line JJ compared to normal chondrocytes. Hypoxia and specifically HIF-1a increased CXCR4 and MMP1 expression in JJ cell line and chondrosarcoma invasion in vitro. The hypoxia mediated increase in MMP1 expression and chondrosarcoma invasion could be inhibited by siRNA directed at HIF-1a or CXCR4, the CXCR4 inhibitor AMD3100, as well as with ERK inhibitor U0126 and ERK siRNA. Chondrosarcoma cell invasion is increased by hypoxia induced expression of CXCR4 and MMP1 and is mediated by HIF-1a and ERK. Both invasion and MMP1 can be inhibited with CXCR4 blockade, suggesting that CXCR4/SDF1 signaling may be a therapeutic target for chondrosarcoma.
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通过缺氧对趋化因子受体CXCR4的调节。
DOI：
10.1084/jem.20030267
发表时间：
2003-11-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.2
作者：
Ishikawa, Tohru;Nakashiro, Koh-ichi;Hamakawa, Hiroyuki
通讯作者：
Hamakawa, Hiroyuki
DOI：
10.1016/j.bbrc.2006.05.110
发表时间：
2006-07-21
影响因子：
3.1
作者：
Shim, Hyunsuk;Lau, Stephen K.;Liang, Zhongxing
通讯作者：
Liang, Zhongxing
影响因子：
4.7
作者：
Tan, Ching-Ting;Chu, Chia-Yu;Kuo, Min-Liang
通讯作者：
Kuo, Min-Liang
影响因子：
11.5
作者：
Laverdiere, C;Hoang, BH;Gorlick, R
通讯作者：
Gorlick, R