Down-regulation of CXCL1 inhibits tumor growth in colorectal liver metastasis
Down-regulation of CXCL1 inhibits tumor growth in colorectal liver metastasis
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DOI：
10.1016/j.cyto.2011.10.019
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发表时间：
2012-01-01
期刊：
影响因子：
3.8
通讯作者：
Brand, Karsten
中科院分区：
文献类型：
--
作者：
Bandapalli, Obul R.;Ehrmann, Franziska;Brand, Karsten
作为正在进行的研究的一部分，以获得结肠直肠癌肝转移侵袭相关事件的全球图景，在这里，我们报告了趋化因子的促血管生成亚群，CXCL-ELR+趋化因子的基因表达的研究结果。除了它们的促血管生成和趋化功能外，这些趋化因子似乎还有助于肿瘤细胞的转化、生长和侵袭。在我们的大肠癌肝转移裸鼠模型中，我们发现与肿瘤内部的肿瘤细胞相比，侵袭前部肿瘤细胞中的CXCL1、2、3、5和8 （IL-8）表达上调。ShRNA介导的最显著上调组成员CXCL1/gro- α的下调导致细胞活力、侵袭和增殖受到抑制。在体内，下调CXCL1几乎完全阻止了裸鼠肿瘤的生长。在机制上，NF-kappaB和Akt参与了CXCL1的促肿瘤功能。(C) 2011 Elsevier Ltd.版权所有。
As part of ongoing studies to obtain a global picture of invasion related events in colorectal liver metastases, here, we report our findings on gene expression of the pro-angiogenic subgroup of chemokines, the CXCL-ELR+ chemokines. Apart from their pro-angiogenic and chemoattractant function, these chemokines appear to also contribute to tumor cell transformation, growth and invasion. In our nude mouse model of colorectal liver metastases, we found CXCL1,2,3,5 and 8 (IL-8) to be up-regulated in the tumor cells of the invasion front as compared to the tumor cells in the inner parts of the tumor. ShRNA mediated down-regulation of the most prominently up-regulated group member, CXCL1/gro-alpha resulted in inhibition of cell viability, invasion and proliferation. In vivo, down-regulation of CXCL1 resulted in a nearly complete prevention of tumor growth in nude mice. Mechanistically, auto-regulatory mechanisms involving NF-kappaB and Akt appear to be involved in pro-tumorigenic functions of CXCL1. (C) 2011 Elsevier Ltd. All rights reserved.