T-box transcription factor Brachyury in lung cancer cells inhibits macrophage infiltration by suppressing CCL2 and CCL4 chemokines.
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.
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, NO. 415 Fengyang Road, Shanghai, 200003, China.
Su
S
Chen
Jian
J
Jiao
Dongjie
D
Jiang
Zongmiao
Z
Wan
Lei
L
Li
Ke
K
Li
Leqin
L
Xu
Zhenhua
Z
Zhou
Wei
W
Xu
Jianru
J
Xiao
D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D054407:Chemokine CCL4 / Q000096:biosynthesis* / Q000235:genetics; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D005326:Fetal Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics*; D000098908:Brachyury Protein
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C111835:CCL2 protein, human; C066507:CCL4 protein, human; C114753:CXCL10 protein, human