title: Inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma.
abstract: OBJECTIVE
  To study the inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma (HCC) in nude mice.
  
  
  METHODS
  CBRH-7919 HCC cells were injected into the subcutaneous region of nude mice. Beginning two weeks after the challenge, tumor growth was measured every week for six weeks. The stromal microenvironment and inflammatory cell infiltration was assessed by immunohistochemistry in paired tumor and adjacent peritumoral samples, and macrophage phenotype was assessed using double-stain immunohistochemistry incorporating expression of an intracellular enzyme. A chemokine PCR array, comprised of 98 genes, was used to screen differential gene expressions, which were validated by Western blotting. Additionally, expression of identified chemokines was knocked-down by RNA interference, and the effect on tumor growth was assessed.
  
  
  RESULTS
  Inflammatory cell infiltrates are a key feature of adjacent peritumoral tissues with increased macrophage, neutrophil, and T cell (specifically helper and activated subsets) infiltration. Macrophages within adjacent peritumoral tissues express inducible nitric oxide synthase, suggestive of a proinflammatory phenotype. Fifty-one genes were identified in tumor tissues during the progression period, including 50 that were overexpressed (including CXCL1, CXCL2 and CXCL3) and three that were underexpressed (CXCR1, Ifg and Actb). RNA interference of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice and inhibited expression of CXCL2, CXCL3 and interleukin-1β protein.
  
  
  CONCLUSIONS
  These findings suggest that CXCL1 plays a critical role in tumor growth and may serve as a potential molecular target for use in HCC therapy.
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Ke-Qi
authors.initials: KQ
authors.lastname: Han
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Xue-Qun
authors.initials: XQ
authors.lastname: He
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Meng-Yu
authors.initials: MY
authors.lastname: Ma
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Guo
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Han
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Zhang
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Quan-Gang
authors.initials: QG
authors.lastname: Zhu
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Nian
authors.affiliation: Ke-Qi Han, Xue-Qun He, Meng-Yu Ma, Xiao-Dong Guo, Xue-Min Zhang, Jie Chen, Hui Han, Wei-Wei Zhang, Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200336, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Ma
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D054360:Chemokine CXCL1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000067492:RNAi Therapeutics; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D047368:Tumor Burden; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D018925:Chemokines
keywords: Chemokines; Gene expression profile; Hepatocellular carcinoma; PCR array; RNA interference