title: Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer.
abstract: The CX3CR1/CX3CL1 axis is involved in the metastasis and prognosis of many types of cancer; however, whether CX3CR1 is expressed in gastric cancer cells and whether it participates in gastric cancer metastasis remain unknown. We investigated the expression of CX3CR1 in gastric cancer tissues and non‑neoplastic gastric tissues in vivo and in gastric cancer cell lines and a gastric epithelial cell line in vitro, and then the functional roles of CX3CR1 in cellular metastasis, proliferation and survival were explored. We observed that CX3CR1 was highly expressed in gastric cancer tissues in vivo and was related to lymph node metastasis, higher clinical TNM stage and larger tumor size. In vitro, CX3CR1 overexpression promoted gastric cancer cell migration, invasion, proliferation and survival. Additionally, different from several chemokine receptors, CX3CR1 was also expressed in non-neoplastic gastric tissues and in gastric epithelial cells and played a functional role in vitro. Notably, gastric cancer tissues expressed higher CX3CR1 compared with that in the non-neoplastic gastric tissues in vivo, while in vitro, CX3CR1 expresssion in the gastric cancer cell lines was equivalent or significantly lower than that in the gastric epithelial cell line, which suggests that the high expression of CX3CR1 in gastric cancer in vivo might be induced, not constitutive. Altogether, our findings suggest that on the one hand overexpression of CX3CR1 promoted gastric cancer metastasis, proliferation and survival; on the other hand, appropriate expression of CX3CR1 in normal gastric tissues may play a physiological role in tissue remodeling after injury and/or epithelial renewal. Additionally, the tumor microenvironment may play an important role in the high expression of CX3CR1 in gastric cancer cells.
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Lu-Min
authors.initials: LM
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Jing-Tong
authors.initials: JT
authors.lastname: Wang
mesh_terms: D000368:Aged; D000073883:CX3C Chemokine Receptor 1; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine