Tumor-induced suppression of marrow stromal colonies

Abstract

The studies reported in this paper evaluated one of the mechanisms by which extramedullary tumor caused anemia, neutrophilia, medullary erythroblastopenia, and suppression of marrow stromal cells (MSC) in tumor bearing mice. Since MSC have been shown to support hemopoiesis, we asked whether tumor released a suppressor which directly inhibited MSC colonies, and if it did, whether or not it was prostaglandin-E (PGE). We found that co-culture of Ehrlich ascites carcinoma (EAC) and Sarcoma (S-180) cells with normal mouse bone marrow cells profoundly suppressed formation of MSC colonies. At concentrations exceeding 15% of the medium, tumor-conditioned media not only suppressed MSC colonies but also enhanced the growth of granulocyte-macrophage colonies (CFUC) in vitro like Colony Stimulating Factor (CSF) from other sources. It did not suppress CFUE, nor did it inhibit growth or kill cells other than MSC in bone marrow cultures. Fibroblasts grew luxuriantly in 20% conditioned media from Ehrlich ascites carcinoma cells. Concentrations of PGE2 required to suppress MSC colonies greatly exceeded those detected in media conditioned by S-180. Production of PGE by S-180 cells was inhibited by growing the tumor cells in the presence of indomethacin, but the supernatant media, devoid of PGE, still markedly suppressed the growth of MSC from normal marrow. Because tumor produced CSF, we tested the suppressive effect of CSF in post-endotoxin serum to find that concentrations of 10 to 15% inhibited MSC colony growth. The results show that these tumors produced a substance, possibly CSF, that selectively inhibited MSC colony growth in vitro. It is conceivable that suppression of the supportive tissue (MSC) for erythropoiesis in the bone marrow by tumor led to diminished erythroblasts in that site.