Tumor Biology

, Volume 36, Issue 8, pp 5881–5890 | Cite as

T-box transcription factor Brachyury in lung cancer cells inhibits macrophage infiltration by suppressing CCL2 and CCL4 chemokines

  • Su Chen
  • Jian Jiao
  • Dongjie Jiang
  • Zongmiao Wan
  • Lei Li
  • Ke Li
  • Leqin Xu
  • Zhenhua Zhou
  • Wei Xu
  • Jianru Xiao
Research Article


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.


Brachyury Lung cancer Chemokine Macrophage infiltration 



This study Project is supported by the National Natural Science Foundation of China (Grant No. 81102036)

Conflicts of interest


Supplementary material

13277_2015_3260_MOESM1_ESM.pdf (15 kb)
Supplementary Table 1 Patient information of the specimens enrolled in the study. Case numbers were determined upon hospitalization. M stands for male; F stands for female and the ages were as shown. The diagnosis and the location of the tumors are recorded. TNM stage was determined equivalent to American Joint Committee of Cancer-AJCC staging standard. Scoring of the IHC staining was recorded as the average score from three independent pathologists’ analysis. (PDF 15 kb)
13277_2015_3260_MOESM2_ESM.pdf (30 kb)
Supplementary Figure 1 Differential expression level of Brachyury in lung cancer cell lines. A. Semi-quantitative RT-PCR was done to test the expression level in the lung cancer cell lines as indicated. Samples were retrieved after 30 cycles of PCR amplification. 18S ribosome RNA was used as loading control to ensure equal loading of each sample. B. Western Blot result of Brachyury expression in the cell lines shown. GAPDH was blotted as loading control. (PDF 30 kb)
13277_2015_3260_MOESM3_ESM.pdf (34 kb)
Supplementary Figure 2 Generation of H460 cells with stable knockdown of BrachyuryandH1299 cell line with overexpression of Brachyury. A. Semi-quantitative RT-PCR of Brachyury expression in H460 cells transfected with control shRNAs (H460shN) or Brachyury shRNAs (H460shT). 18S was used as loading control. B. Western blot result testing Brachyury expression in H460shN and H460shT cells. GAPDH was used as loading control. C. RT-PCR examination of Brachyury expression in H1299 cells transfected with empty vector (H1299EV) or Brachyury overexpression plasmid (H1299TOE). 18S was used as loading control. D. Western blot result testing Brachyury expression in H1299EV and H1299TOE cells. GAPDH was used as loading control. (PDF 34 kb)
13277_2015_3260_MOESM4_ESM.pdf (14 kb)
Supplementary Figure 3 The gene list of 84 genes that encode chemokines and their receptors (PDF 13 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Su Chen
    • 1
  • Jian Jiao
    • 1
  • Dongjie Jiang
    • 1
  • Zongmiao Wan
    • 1
  • Lei Li
    • 2
  • Ke Li
    • 2
  • Leqin Xu
    • 1
  • Zhenhua Zhou
    • 1
  • Wei Xu
    • 1
  • Jianru Xiao
    • 1
  1. 1.Department of Bone Tumor Surgery, Changzheng HospitalSecond Military Medical UniversityShanghaiChina
  2. 2.Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical SciencesEast China Normal UniversityShanghaiChina

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