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RASSF1A suppresses the activated K-Ras-induced oxidative DNA damage
Authors:Park Seon Ho  Kim Jung Jin  Chung Jin Sil  Lee So Ra  Lee Gi Young  Kim Hyung Jung  Yoo Young Do
Institution:aCenter for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA;bDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA;cDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Abstract:Dendritic cells are the most potent antigen presenting cells responsible for the development of immune responses in cancer. However, it is known that the function of dendritic cells in tumor-bearing hosts is severely compromised. Our previous studies demonstrated that the defects in dendritic cell function are due, to a large extent, to the accumulation of high amounts of lipids – predominantly triglycerides – in a substantial proportion of dendritic cells in tumor-bearing mice and patients with cancer. The dendritic cells accumulation of lipids is likely associated with their up-regulation of a scavenger receptor A. This receptor is primarily responsible for uptake of modified lipids. Here, by using different versions of liquid chromatography–mass spectrometry, we identified several molecular species of oxygenated lipids in plasma of tumor-bearing animals that may be responsible for their uptake and accumulation by dendritic cells via scavenger receptor A-dependent pathway – the effect that may be associated with the loss of dendritic cell’s immune surveillance function in cancer.
Keywords:Cancer  Tumor-bearing mice  Plasma  Dendritic cells  Scavenger receptor A  Lipid uptake  Oxygenated fatty acids
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