title: CCR7 enhances TGF-β1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer.
abstract: CCR7 is a G protein-coupled chemokine receptor. In this study, we used immunohistochemistry with tissue microarrays to measure CCR7 expression in tumor specimens from 122 patients with gastric cancer. We show that CCR7 expression is associated with lymph node metastasis (P = 0.022) and overall survival (OS; P = 0.025), and is an independent factor associated with poorer overall survival (P = 0.032). The CCR7 mechanism was predicted based on bioinformatic analysis and verified in gastric cancer cell lines and primary tumor samples. The data show that CCR7 contributes to TGF-β1-induced epithelial-mesenchymal transition (EMT) and that the effects of TGF-β1 are inhibited by a CCR7 neutralizing antibody or a NF-κB inhibitor. Increased TGF-β1 expression was accompanied by nuclear localization of NF-κB-p65 and higher levels of the mesenchymal marker vimentin in human gastric cancer samples. We conclude that the CCR7 axis mediates TGF-β1-induced EMT via crosstalk with NF-κB signaling, facilitating lymph node metastasis and poorer overall survival in patients with gastric cancer. These findings suggest CCR7 is a novel prognostic indicator and a potential target for gastric cancer therapy.
authors.affiliation: Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Gao
authors.affiliation: The General Surgery Department of Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Xinzhou
authors.initials: X
authors.lastname: Liu
authors.affiliation: The General Surgery Department of Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.|The Department of Anatomy and Histology & Embryology, Tongji University School of Medicine, Shanghai, P. R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhou
authors.affiliation: The Liver Cancer Institute of Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.affiliation: The Liver Cancer Institute of Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Liu
authors.affiliation: The General Surgery Department of Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.
authors.forename: Chunmin
authors.initials: C
authors.lastname: Liang
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010641:Phenotype; D011379:Prognosis; D054400:Receptors, CCR7 / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014746:Vimentin
keywords: CCR7; TGF-β1; co-stimulatory; epithelial-mesenchymal transition; gastric cancer