Density-dependent tumor cell death and reversible cell cycle arrest: mutually exclusive modes of monocyte-mediated growth control.
The population development of five human tumor cell lines is examined under the influence of elutriator-prepared human monocytes in a serum-free hormone- and growth factor-supplemented medium. Analysis was performed by electronic counting and sizing of tumor cell nuclei and flow cytometric detection of cell cycle phases. Tumor cell death is triggered at rather low monocyte:tumor cell ratios (1:2 to 1:4) whereas it is strongly reduced at high monocyte densities. Furthermore, it is shown that confluence of the target cell population is a necessary prerequisite for lysis. The data suggest that in monocyte/tumor cell cocultures the decision on target cell lysis is not made by the effector cell, but rather by the target cell and that the criterion for this decision is the target cell's ability or inability to respond to a monocyte challenge by arresting the cell cycle in G1. Interactions between target cells play an important role in determining the result of this decision process. A common basis is suggested for this kind of density-dependent monocyte-triggered lysis and density-dependent cell death in 3T3 cell cultures as described previously.
van der Bosch
J
J
Forschungsinstitut Borstel, Institut für Experimentelle Biologie und Medizin, Federal Republic of Germany.
Rüller
S
S
Horn
D
D
Schumann
R
R
Schlaak
M
M
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007624:KB Cells; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma