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- W1999533042 abstract "The leukocyte composition of tumors is heterogeneous, as is the involvement of each leukocyte subset in promoting or restraining tumorigenesis. This heterogeneity reflects the tissue of origin, tumor stage, and the functional state of leukocyte activation, but its biological roots remain poorly understood. Since tumorigenesis is driven by various genetic events, we assessed the role of driver genes in shaping the profiles and the roles of leukocytes in tumorigenesis.Mouse liver tumors were induced by hepatic overexpression of either MYC or the combination of myristoylated AKT and NRASV12 oncogenes via hydrodynamic transfection. A comparative, flow cytometry- and histology-based immunophenotyping of liver-infiltrating leukocytes was performed at various stages of liver tumorigenesis. The roles of the most abundant leukocyte subsets in tumorigenesis were addressed by immunodepletion. The contribution of liver injury was assessed by comparing the injury-inducing hydrodynamic transfection model to a model in which MYC is an inducible transgene.Myristoylated AKT and NRASV12 promoted a marked recruitment of CD11b+Ly6GhiLy6Cint neutrophils and CD11b+Ly6G−Ly6Chi monocytes to the liver, but their immunodepletion did not alter tumorigenesis. In contrast, despite minimal invasion by monocytes/neutrophils during MYC-driven tumorigenesis, immunodepletion of these cells reduced MYC tumor burden and extended survival. MYC-driven tumor initiation was augmented specifically by Ly6C+ monocytes and their ability to promote liver injury.Our results demonstrate that leukocyte profiles do not necessarily predict their involvement in tumorigenesis, the functional role of leukocytes can be shaped by oncogenes, and that monocyte-dependent tissue injury selectively cooperates with MYC during tumorigenesis." @default.
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- W1999533042 date "2014-09-01" @default.
- W1999533042 modified "2023-10-16" @default.
- W1999533042 title "Aqueous cigarette smoke extract promotes the adhesion of monocytic cells to human coronary artery endothelial cells in direct and indirect-dependent ways" @default.
- W1999533042 doi "https://doi.org/10.1016/j.toxlet.2014.06.300" @default.
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