title: Gene expression and tumor cell escape from host effector mechanisms in murine large cell lymphoma.
abstract: Using in vivo selection methods, we obtained metastatic sublines of the murine RAW117 large cell lymphoma that form multiple liver metastases. The highly metastatic subline RAW117-H10 has a low number of gp70 molecules expressed at the cell surface and low cytostatic sensitivity to activated syngeneic macrophages. This subline was infected with endogenous RNA tumor virus isolated from a high virus-expressing RAW117-P subline of low metastatic potential. After superinfection the H10 subline gradually increased its expression of cell surface gp70 and showed enhanced sensitivity to macrophage-mediated cytostasis, suggesting that gp70 might be involved in host macrophage-mediated surveillance. Culture of RAW117-P and H10 cells in media conditioned by activated macrophages indicated that parental cells are severely growth inhibited in a dose dependent fashion while H10 cells showed almost no effect. Examination of differentially expressed genes in the highly metastatic RAW117-H10 cells by analysis of RNA blots indicated that a mitochondrial gene was expressed at a level that was approximately 10 times higher in H10 cells than in parental cells. This gene was identified as ND5, which codes for a subunit of NADH dehydrogenase (complex I of the mitochondrial electron transport chain); this complex is the target for an activated macrophage-released cytostatic factor. Among other possibilities, the results are consistent with the suggestion that highly metastatic RAW117 cells may escape macrophage surveillance by decreasing the synthesis of specific cell-surface receptors for cytostatic molecules and increasing the synthesis of specific cellular targets for such molecules.
authors: Department of Tumor Biology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030.
authors: R A
authors: RA
authors: LaBiche
authors: M
authors: M
authors: Yoshida
authors: G E
authors: GE
authors: Gallick
authors: T
authors: T
authors: Irimura
authors: D L
authors: DL
authors: Robberson
authors: J
authors: J
authors: Klostergaard
authors: G L
authors: GL
authors: Nicolson
mesh_terms: D000818:Animals; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation; D007157:Immunologic Surveillance; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000556:secondary; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D008562:Membrane Glycoproteins