T-box transcription factor Brachyury in lung cancer cells inhibits macrophage infiltration by suppressing CCL2 and CCL4 chemokines
T-box transcription factor Brachyury in lung cancer cells inhibits macrophage infiltration by suppressing CCL2 and CCL4 chemokines
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肺癌细胞中的 T-Box 转录因子 Brachyury 通过抑制 CCL2 和 CCL4 趋化因子来抑制巨噬细胞浸润
DOI：
10.1007/s13277-015-3260-2
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发表时间：
2015-08-01
期刊：
影响因子：
--
通讯作者：
Xiao, Jianru
中科院分区：
文献类型：
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作者：
Chen, Su;Jiao, Jian;Xiao, Jianru
肿瘤内巨噬细胞和T-box转录因子Brachyury (T)已被证明在肿瘤进展和转移中发挥重要作用。然而，T是否能调节巨噬细胞的浸润，尚不清楚。在这里，我们报道了Brachyury在人肺肿瘤中的表达与巨噬细胞的浸润呈负相关。Brachyury抑制人肺癌细胞吸引巨噬细胞的能力。通过PCR阵列，我们发现Brachyury抑制了几种趋化因子的表达，包括CCL2、CCL4和CXCL10。因此，在共培养条件下，肺癌细胞中CCL2和CCL4的下调抑制了巨噬细胞的侵袭。此外，我们发现Brachyury在人肺肿瘤中的表达与CCL2和CCL4的表达呈负相关。综上所述，我们的发现揭示了Brachyury在巨噬细胞浸润调节中的新作用。
Both intra-tumor macrophage and T-box transcription factor Brachyury (T) have been proved to play important roles in tumor progression and metastasis. However, it is still unknown whether T could regulate the infiltration of macrophages. Here, we report that the Brachyury expression in human lung tumors was inversely correlated with the infiltration of macrophages. Brachyury suppressed the capability of human lung cancer cells to attract macrophages. Using PCR array, we found that Brachyury inhibited expression of several chemokines, including CCL2, CCL4, and CXCL10. Accordingly, knockdown of CCL2 and CCL4 in lung cancer cells suppressed macrophage invasion under coculture conditions. Furthermore, we found that Brachyury expression was inversely correlated with CCL2 and CCL4 expression in human lung tumors. Taken together, our findings shed light on the novel role of Brachyury in regulation of macrophage infiltration.