Abstract
BackgroundApolipoprotein 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.MethodsCryo 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.ResultsApoA-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.ConclusionOur data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities.
Highlights
Serum apolipoprotein A-II (ApoA-II) was found to be depressed in pancreatic cancer patients and was a potential diagnostic biomarker [1]
Apolipoprotein A-II Plus Lipid Emulsion Target Pancreatic Cancer affiliation of the authors at CSIRO did not play any role in the study and did not have any competing interests relating to employment, consultancy, patents, products in development and marketed products
Commercial affiliation of the authors at CSIRO did not play any role in the study and did not have any competing interests relating to employment, consultancy, patents, products in development and marketed products
Summary
Serum apolipoprotein A-II (ApoA-II) was found to be depressed in pancreatic cancer patients and was a potential diagnostic biomarker [1]. ApoA-II is a component of high density lipoprotein (HDL) where it has an important role in directing the fate of the metabolism of the lipid in the HDL. The role of cholesterol metabolism in the process of carcinogenesis is reported [22,23,24].Cancer and other rapidly proliferating cells require cholesterol and other membrane components to optimize growth [25]. 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
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