title: N-methyl-N-nitro-N'-nitrosoguanidine induces the expression of CCR2 in human gastric epithelial cells promoting CCL2-mediated migration.
abstract: Chronic inflammation has a decisive role in tumorigenesis, particularly in gastric carcinogenesis. The CC chemokine ligand 2 (CCL2), an important inflammatory cytokine, is involved in the initiation, development and progression of various types of cancer. However, the role of CCL2 in gastric cancer remains to be elucidated. The present study demonstrated that recombinant CCL2 stimulation caused no effect on the morphology, proliferation and migration of human GES-1 gastric mucosa epithelial cells, in which the protein expression of CC-chemokine receptor 2 (CCR2) was markedly low. However, the expression of CCR2 was significantly upregulated in the GES-1 cells following pretreatment with the chemical carcinogen, N-methyl-N-nitro-N'-nitrosoguanidine (MNNG), for 12 h or transformed with MNNG (MC cells). The present study used CCL2 to stimulate MNNG pretreated GES-1 cells and MC cells, and demonstrated that CCL2 clearly promoted their migration and the epithelial-mesenchymal transition (EMT). However, no effect was observed on the proliferative ability of the cells. Taken together, these findings suggested that the CCL2/CCR2 chemokine signaling may regulate the EMT in gastric epithelial cells and resulted in gastric carcinogenesis in response to the intake of the carcinogen, MNNG.
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Mengchu
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Wenrong
authors.initials: W
authors.lastname: Xu
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D018932:Chemokine CCL2 / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000378:metabolism*; D013270:Stomach / Q000166:cytology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D008769:Methylnitronitrosoguanidine