Prostaglandin E and the erythropoietic and stromal insufficiency induced by extramedullary tumor.
This paper reports the results of our studies concerning the specificity and mechanism of anemia in tumor-bearing mice. Three different types of transplanted extramedullary tumors, including a carcinoma (EAC), a sarcoma (S-180), and a leukemia (L-1210) produced anemia, neutrophilia, and medullary erythroblastopenia. Because the most striking effects were observed with S-180, it was selected for detailed study. Although erythroblasts were greatly decreased in the bone marrow to about 1% in the differential count, CFU-E and BFU-E were not, suggesting inhibited maturation of erythroid progenitors. Suppression of MSC to 1/3 of normal occurred at 21 days of tumor bearing, and qualitatively abnormal MSC at 35 days failed to enhance CFU-E and BFU-E in split-phase culture. We found that these MSC from tumor-bearing mice produced suppressive levels of PGE. PGE production and erythroid colony enhancement of MSC from either normal or tumor-bearing mice was abrogated by including 5 micrograms/ml indomethacin in the split-phase culture. Medium conditioned by S-180 that was capable of suppressing the growth of MSC colonies had no direct effect on erythroid colony formation. Our results support a hypothesis that extramedullary tumors are capable of producing a lesion in the supportive tissue of the bone marrow, leading to anemia and medullary erythroblastopenia. We believe that early, the tumor suppresses the number of MSC required for maturation of erythroid precursors and later induces the normal numbers of MSC to produce suppressive levels of PGE.
D000818:Animals; D001854:Bone Marrow Cells; D002286:Carcinoma, Ehrlich Tumor / Q000503:physiopathology; D004920:Erythropoiesis; D007942:Leukemia, Experimental / Q000503:physiopathology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000503:physiopathology*; D011458:Prostaglandins E / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000503:physiopathology
D011458:Prostaglandins E