Gene expression and tumor cell escape from host effector mechanisms in murine large cell lymphoma.
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.
LaBiche
R A
RA
Department of Tumor Biology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Yoshida
M
M
Gallick
G E
GE
Irimura
T
T
Robberson
D L
DL
Klostergaard
J
J
Nicolson
G L
GL
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
D008562:Membrane Glycoproteins