title: Apolipoprotein A-II Plus Lipid Emulsion Enhance Cell Growth via SR-B1 and Target Pancreatic Cancer In Vitro and In Vivo.
abstract: BACKGROUND
  Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization of high density lipoprotein (HDL) lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC) both in vitro and in vivo.
  
  
  METHODS
  Cryo transmission electron microscopy (TEM) examined ApoA-II's influence on morphology of SMOFLipid emulsion. The influence of ApoA-II on proliferation of cancer cell lines was determined by incubating them with lipid+/-ApoA-II and anti-SR-B1 antibody. Lipid was labeled with the fluorophore, DiD, to trace lipid uptake by cancer cells in vitro by confocal microscopy and in vivo in PDAC patient derived xenograft tumours (PDXT) by fluorescence imaging. Scavenger receptor class B type-1(SR-B1) expression in PDAC cell lines and in PDAC PDXT was measured by western blotting and immunohistochemistry, respectively.
  
  
  RESULTS
  ApoA-II spontaneously converted lipid emulsion into very small unilamellar rHDL like vesicles (rHDL/A-II) and enhanced lipid uptake in PANC-1, CFPAC-1 and primary tumour cells as shown by confocal microscopy. SR-B1 expression was 13.2, 10.6, 3.1 and 2.3 fold higher in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cell lines than the normal pancreatic cell line (HPDE6) and 3.7 fold greater in PDAC tissue than in normal pancreas. ApoA-II plus lipid significantly increased the uptake of labeled lipid and promoted cell growth in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cells which was inhibited by anti SR-B1 antibody. Further, ApoA-II increased the uptake of lipid in xenografts by 3.4 fold.
  
  
  CONCLUSIONS
  Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities.
authors.affiliation: Cancer Surgery Group, Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: Sohel M
authors.initials: SM
authors.lastname: Julovi
authors.affiliation: Cancer Surgery Group, Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Xue
authors.affiliation: Cancer Surgery Group, Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: Thao N
authors.initials: TN
authors.lastname: Thanh LE
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research,University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.affiliation: Cancer Surgery Group, Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia.|CSIRO Manufacturing, CSIRO, North Ryde, New South Wales, Australia.
authors.forename: Jerikho C
authors.initials: JC
authors.lastname: Bulanadi
authors.affiliation: Centre for Vascular Research, Faculty of Medicine, University of New South Wales, New South Wales, Australia.
authors.forename: Mili
authors.initials: M
authors.lastname: Patel
authors.affiliation: CSIRO Manufacturing, CSIRO, Parkville, Victoria, Australia.
authors.forename: Lynne J
authors.initials: LJ
authors.lastname: Waddington
authors.affiliation: Centre for Vascular Research, Faculty of Medicine, University of New South Wales, New South Wales, Australia.
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.affiliation: CSIRO Manufacturing, CSIRO, North Ryde, New South Wales, Australia.
authors.forename: Minoo J
authors.initials: MJ
authors.lastname: Moghaddam
authors.affiliation: Cancer Surgery Group, Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia.|Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: Ross C
authors.initials: RC
authors.lastname: Smith
mesh_terms: D016633:Apolipoprotein A-II / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D006801:Humans; D008055:Lipids / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000378:metabolism; D061986:MCF-7 Cells; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000378:metabolism*
chemical_list: D016633:Apolipoprotein A-II; D008055:Lipids; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B