title: Activated hepatic stellate cells promote angiogenesis via interleukin-8 in hepatocellular carcinoma.
abstract: BACKGROUND
  Chemokines have been recognized as important modulators of angiogenesis, and they play critical roles in the development and metastasis of hepatocellular carcinoma (HCC), although their origins and latent molecular mechanisms remain elusive. The aim of this study was to investigate how activated hepatic stellate cells (a-HSCs) promote angiogenesis in HCC.
  
  
  METHODS
  A total of 22 HCC patients were enrolled randomly. We used immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay (ELISA) to analyse the production of interleukin-8 (IL-8) in a-HSCs derived from HCC tissues. The angiogenic effects of IL-8 in vitro and in vivo were assessed by ELISA, real-time quantitative polymerase chain reaction, capillary tube formation assay, and chick embryo chorioallantoic membrane assay.
  
  
  RESULTS
  The present study showed that IL-8 was enriched predominantly in the tumour stroma of HCC tissues and was mainly derived from a-HSCs, rather than from hepatoma cells, in vivo and in vitro. Angiogenesis was most active at the invading edge, which was close to the a-HSCs. The angiogenic effect was dramatically attenuated by an IL-8 neutralizing antibody both in vitro and in vivo. Moreover, the IL-8 neutralizing antibody down-regulated Ser727-phosphorylated STAT3 levels in hepatoma cells treated with a-HSCs conditioned medium.
  
  
  CONCLUSIONS
  These findings reveal that a-HSCs within the stroma of HCC contribute to tumour angiogenesis via IL-8.
authors.affiliation: Department of Hepatobiliary Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, China. bbmczhubing@163.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, China. drlinnan@vip.163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Lin
authors.affiliation: Department of Infectious Diseases, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. zm20051208@163.com.|Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China. zm20051208@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, The 4th Affiliated Hospital of Anhui Medical University, Hefei, China. zhuyong0831@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 544657716@qq.com.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Hepatobiliary Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, China. mousech7048@163.com.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, China. 1353018679@qq.com.
authors.forename: Yunbiao
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Hepatobiliary Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, China. 1710688166@qq.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Hepatobiliary Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, China. drxuruiyun@163.com.
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Xu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply*; D002642:Chick Embryo; D004797:Enzyme-Linked Immunosorbent Assay; D055166:Hepatic Stellate Cells / Q000166:cytology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000502:physiology*; D008113:Liver Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic
chemical_list: D057134:Antibodies, Neutralizing; D016209:Interleukin-8