title: Low level of low-density lipoprotein receptor-related protein 1 predicts an unfavorable prognosis of hepatocellular carcinoma after curative resection.
abstract: BACKGROUND
  Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in receptor-mediated endocytosis and cell signaling. The aim of this study was to elucidate the expression and mechanism of LRP1 in hepatocellular carcinoma (HCC).
  
  
  METHODS
  LRP1 expression in 4 HCC cell lines and 40 HCC samples was detected. After interruption of LRP1 expression in a HCC cell line either with specific lentiviral-mediated shRNA LRP1 or in the presence of the LRP1-specific chaperone, receptor-associated protein (RAP), the role of LRP1 in the migration and invasion of HCC cells was assessed in vivo and in vitro, and the expression of matrix metalloproteinase (MMP) 9 in cells and the bioactivity of MMP9 in the supernatant were assayed. The expression and prognostic value of LRP1 were investigated in 327 HCC specimens.
  
  
  RESULTS
  Low LRP1 expression was associated with poor HCC prognosis, with low expression independently related to shortened overall survival and increased tumor recurrence rate. Expression of LRP1 in non-recurrent HCC samples was significantly higher than that in early recurrent samples. LRP1 expression in HCC cell lines was inversely correlated with their metastatic potential. After inhibition of LRP1, low-metastatic SMCC-7721 cells showed enhanced migration and invasion and increased expression and bioactivity of MMP9. Correlation analysis showed a negative correlation between LRP1 and MMP9 expression in HCC patients. The prognostic value of LRP1 expression was validated in the independent data set.
  
  
  CONCLUSIONS
  LRP1 modulated the level of MMP9 and low level of LRP1 expression was associated with aggressiveness and invasiveness in HCCs. LRP1 offered a possible strategy for tumor molecular therapy.
authors.affiliation: Liver Cancer Institute, Fudan University, Zhongshan Hospital, Shanghai, People's Republic of China.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Huang
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Shi
authors.forename: Ranjan Prasad
authors.initials: RP
authors.lastname: Devbhandari
authors.forename: Ai-Wu
authors.initials: AW
authors.lastname: Ke
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Shi
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Xiao
authors.forename: Zhen-Bin
authors.initials: ZB
authors.lastname: Ding
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dai
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Jia
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000601:surgery; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002681:China; D017931:DNA Primers / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D026563:LDL-Receptor Related Protein-Associated Protein / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000601:surgery; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D046228:Microarray Analysis; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D026563:LDL-Receptor Related Protein-Associated Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D034741:RNA, Small Interfering; D020780:Matrix Metalloproteinase 9