By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization.
By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization.
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通过激活基质金属蛋白酶7，剪切应力促进软骨肉瘤细胞运动、侵袭和肺部定植
DOI：
10.18632/oncotarget.3274
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发表时间：
2015-04-20
期刊：
影响因子：
--
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Guan PP;Yu X;Guo JJ;Wang Y;Wang T;Li JY;Konstantopoulos K;Wang ZY;Wang P
间质流体流动和相关的剪切应力是软骨和骨（病理）生理学中的相关机械信号。然而，它们对软骨肉瘤细胞运动、侵袭和转移的影响还有待阐明。以人SW 1353、HS. 819. T和CH 2879软骨肉瘤细胞系为模型系统，我们发现流体切应力诱导细胞内cAMP和IL-1 β的积累，进而通过诱导基质金属蛋白酶-7（MMP-7）而显著增强软骨肉瘤细胞的运动和侵袭能力。具体而言，剪切诱导的cAMP和IL-1β激活PI 3-K、ERK 1/2和p38信号通路，其通过反式激活人软骨肉瘤细胞中的NF-κB和c-Jun而导致MMP-7的合成。重要的是，剪切应力暴露后MMP-7的上调能够促进体内软骨肉瘤的肺定植。这些研究结果提供了一个更好的理解的机制MMP-7激活剪切刺激软骨肉瘤细胞，并提供新的治疗策略，以干扰软骨肉瘤的侵袭和转移的见解。
Interstitial fluid flow and associated shear stress are relevant mechanical signals in cartilage and bone (patho)physiology. However, their effects on chondrosarcoma cell motility, invasion and metastasis have yet to be delineated. Using human SW1353, HS.819.T and CH2879 chondrosarcoma cell lines as model systems, we found that fluid shear stress induces the accumulation of cyclic AMP (cAMP) and interleukin-1β (IL-1β), which in turn markedly enhance chondrosarcoma cell motility and invasion via the induction of matrix metalloproteinase-7 (MMP-7). Specifically, shear-induced cAMP and IL-1β activate PI3-K, ERK1/2 and p38 signaling pathways, which lead to the synthesis of MMP-7 via transactivating NF-κB and c-Jun in human chondrosarcoma cells. Importantly, MMP-7 upregulation in response to shear stress exposure has the ability to promote lung colonization of chondrosarcomas in vivo. These findings offer a better understanding of the mechanisms underlying MMP-7 activation in shear-stimulated chondrosarcoma cells, and provide insights on designing new therapeutic strategies to interfere with chondrosarcoma invasion and metastasis.
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影响因子：
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作者：
Bae GY;Choi SJ;Lee JS;Jo J;Lee J;Kim J;Cha HJ
通讯作者：
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影响因子：
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作者：
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影响因子：
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通讯作者：
DOCHERTY, A
DOI：
10.1016/j.biocel.2007.06.013
发表时间：
2007-01-01
影响因子：
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作者：
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通讯作者：
Pannen, Benedikt H. J.