Cancer cell inhibition of erythropoiesis.

In this study we have used tissue culture techniques to explore the mechanism by which metastatic cancer cells in the bone marrow interfere with erythropoiesis. The effect of transplantable Walker-256 (W256) cancer cells on Ep-stimulated erythroid colony formation (CFU-E) in methylcellulose cultures and 59Fe-heme synthesis by rat marrow cells in suspension cultures was studied. The number of CFU-Es per 4 X 10(5) marrow cells decreased by 55% in the presence of 4 X 10(2) cancer cells. Likewise, the stimulatory effect of Ep on normal marrow heme synthesis decreased by 89% when cancer cells were added to marrow cell cultures. By the immobilization of the cancer cells in an agar underlayer, the inhibitory effect of cancer cells on marrow erythropoiesis in an upper methylcellulose layer was demonstrated to be independent of cell contact. The CFU-E growth-inhibitory effect of cancer cells could be attenuated by drugs which interfere with cancer cell protein and DNA synthesis. Although these experiments suggest that cancer cells produce an inhibitor of erythropoiesis, a stable inhibitory factor was not isolated. In similar experiments, rat peritoneal macrophages were also able to inhibit in vitro erythropoiesis. We conclude that cancer cells have the capacity to inhibit erythropoiesis by a mechanism which is independent of cell contact.