title: Effects of benzo[a]pyrene exposure on human hepatocellular carcinoma cell angiogenesis, metastasis, and NF-κB signaling.
abstract: BACKGROUND
  Benzo[a]pyrene (B[a]P) is a common environmental and foodborne pollutant. Although the carcinogenicity of high-dose B[a]P has been extensively reported, the effects of long-term B[a]P exposure at lower environmental doses on cancer development are less understood.
  
  
  OBJECTIVE
  We investigated the impact of B[a]P on human hepatocellular carcinoma (HCC) progression at various levels of exposure and identified a potential intervention target.
  
  
  METHODS
  We used a model based on human HCC cells exposed to various concentrations of B[a]P (i.e., 0.01, 1, or 100 nM) for 1 month to examine the effects of B[a]P on cell growth, migration, invasion, and angiogenicity. A bioluminescent murine model was established to assess tumor metastasis in vivo.
  
  
  RESULTS
  Chronic B[a]P exposure did not alter HCC cell growth but promoted cell migration and invasion both in vitro and in vivo. There was an negative association between B[a]P exposure and the survival of tumor-bearing mice. In addition, B[a]P-treated HCC cells recruited vascular endothelial cells and promoted tumor angiogenesis, possibly through elevating vascular endothelial growth factor secretion. Furthermore, the NF-κB pathway may be an adverse outcome pathway associated with the cumulative effects of B[a]P on HCC metastasis.
  
  
  CONCLUSIONS
  These findings a) indicate that B[a]P has effects on HCC progression; b) identify a possible adverse outcome pathway; and c) contribute to a better understanding of the adverse effects of chronic exposure of B[a]P to human health.
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ba
authors.forename: Junyang
authors.initials: J
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.forename: Hongling
authors.initials: H
authors.lastname: Qiu
authors.forename: Jingquan
authors.initials: J
authors.lastname: Li
authors.forename: Ruiai
authors.initials: R
authors.lastname: Chu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
authors.forename: Yongning
authors.initials: Y
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells; D015386:Hazardous Substances / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D015398:Signal Transduction
chemical_list: D015386:Hazardous Substances; D016328:NF-kappa B; D001564:Benzo(a)pyrene