The effect of the H-4-II-E2 (H4) rat tumor cell line on murine granulocyte/macrophage colony-forming units (CFU-gm) was studied in vitro using a bilayer (agar/methylcellulose) culture system over the tumor cell feeder and 10% colony-stimulating activity (CSA). The H4 cells demonstrated an amplification of CSA from several sources and of CFU-gm growth of murine marrow, including the CSA present in L-cell-conditioned medium (L-CSA; 200% of control). The amplification did not result from CSA produced by the H4 cell line, nor was cell-to-cell contact necessary for enhanced CFU-gm growth. Amplification of L-CSA was not mediated by endogenous or exogenous prostaglandin E concentrations in the in vitro system. Furthermore, incubation of the non-adherent marrow cell population with H4 tumor cells for 24 h prior to assaying for CFU-gm resulted in more colonies, independent of the continued presence of H4 tumor cells. The data suggest that the H4 tumor cells produce a readily diffusable, soluble factor that may amplify the effect of L-CSA on CFU-gm by stimulating a more primitive progenitor cell that expands the CFU-gm population.
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