INTERACTIONS BETWEEN HUMAN MONOCYTES AND TUMOR-CELLS - MONOCYTES CAN EITHER ENHANCE OR INHIBIT THE GROWTH AND SURVIVAL OF K562 CELLS

Human bloodstream monocytes can kill cultured tumour cells (K562), as assessed by specific release of Cr-51 from the targets and by inhibition of H-3-thymidine incorporation, Confluent monolayers of monocytes were required for maximal cytotoxicity, and the density of the K562 cells was also an important factor. For example. when K562 cells were seeded at high cell densities, they were killed during incubation with monocytes, but when seeded at low cell densities their growth and survival was enhanced during culture with monocytes. The factor(s) which promoted the survival and division of low density K562 cultures was endogenously secreted from monocytes as it was present in monocyte-conditioned medium, whereas the cytotoxic factor(s) were only expressed during co-culture of monocytes with K562 cells. Conditioned medium from HL 60, U-937, HeLa and K562 could also enhance the growth and survival of low density K562 cultures, and a similar effect was also observed upon the addition of catalase and superoxide dismutase to such cultures. Thus, the monocyte:target ratio is important in determining whether monocytes exhibit cytotoxic or growth-promoting effects and hence tumour-derived or monocyte-derived reactive oxidant species may play a role in tumour cell cycle regulation.