title: Direct transformation of lung microenvironment by interferon-α treatment counteracts growth of lung metastasis of hepatocellular carcinoma.
abstract: BACKGROUND
  Interferon (IFN)-α is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-α treatment in lung metastasis are not yet clear.
  
  
  METHODS
  The effect of IFN-α treatment was studied by using an orthotopic xenograft model and measuring tumor size and lung metastasis. Pretreatment with IFN-α before implantation of tumor was done to explore the effect of IFN-α on lung tissues. Cytokines and macrophages were measured by immunohistochemistry and/or PCR assay, using human origin or mouse origin primers to differentiate the sources. Circulating tumor cells (CTCs) were also assayed by flow cytometry.
  
  
  RESULTS
  IFN-α treatment did not decrease the number of CTCs (0.075% ± 0.020% versus 0.063%±0.018%, P = 0.574, IFN-α-treated versus control groups), but did decrease the number and size of lung metastasis (number: 1.75 ± 1.0 versus 28.0 ± 6.3, P = 0.008; size [pixels]: 116.8 ± 72.2 versus 5226.4 ± 1355.7, P = 0.020), and inhibited macrophage infiltration (0.20% ± 0.04% versus 1.36% ± 0.21%, P = 0.0058) and alteration of matrix metalloproteinase (MMP)-9 expression (mean integrated optical density (IOD): 5.1 ± 1.7 versus 21.9 ± 0.4, P<0.000) in the lung, which was independent of the primary tumor.
  
  
  CONCLUSIONS
  IFN-α inhibited lung metastasis by directly modulating the lung microenvironment.
authors.affiliation: Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Zhuang
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhu
authors.forename: Ju-Bo
authors.initials: JB
authors.lastname: Zhang
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009360:Neoplastic Cells, Circulating / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D016898:Interferon-alpha; D020780:Matrix Metalloproteinase 9