title: CXCL5 contributes to tumor metastasis and recurrence of intrahepatic cholangiocarcinoma by recruiting infiltrative intratumoral neutrophils.
abstract: CXCL5 is a member of the CXC-type chemokine family that may play a role in carcinogenesis and cancer progression. This study investigates the biological function and clinical significance of CXCL5 in intrahepatic cholangiocarcinoma (ICC). We demonstrated that CXCL5 was overexpressed in ICC cell lines and tumor samples compared with paired normal tissues. CXCL5 had a direct chemoattractant effect on neutrophils in vitro through PI3K-Akt and extracellular signal-regulated kinase 1/2 signaling pathways. In animal studies, CXCL5 promoted tumor growth and metastasis without altering in vitro proliferative and invasive ability of ICC cells, and this effect was mediated by the recruitment of intratumoral infiltrative neutrophils by tumor-derived CXCL5. Immunohistochemical analysis of ICC samples showed that overexpression of CXCL5 correlated strongly with intratumoral neutrophil infiltration, shorter overall survival and high tumor recurrence. Multivariate analysis revealed that CXCL5 overexpression alone, or combined with the presence of intratumoral neutrophils, was an independent prognostic indicator for ICC. In conclusion, our data showed that CXCL5 promotes ICC growth and metastasis by recruiting intratumoral neutrophils. CXCL5 alone or combined with intratumoral neutrophils is a novel prognostic predictor for ICC patients and a potential therapeutic target.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China and.
authors.forename: Shao-Lai
authors.initials: SL
authors.lastname: Zhou
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dai
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Zhou
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Xiao
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Hu
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Huang
authors.forename: Guo-Huan
authors.initials: GH
authors.lastname: Yang
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Shi
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
mesh_terms: D054365:Chemokine CXCL5 / Q000502:physiology*; D018281:Cholangiocarcinoma / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D009362:Neoplasm Metastasis; D009504:Neutrophils / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C486263:CXCL5 protein, human; D054365:Chemokine CXCL5