Lipoprotein Inhibitor of Bqne Marrow Cells in Tumor‐bearing Rats

Abstract

The role of a plasma inhibitor of erythropoiesis is evaluated in rats with Walker‐256 carcinoma (W‐256). Plasma from tumor‐bearing rats was treated by gel filtration chromatography (Sephadex G‐150) and fractions were combined into four pools on the basis of mol. wt. Inhibitory activity was assayed by adding an aliquot of the plasma fractions to normal rat marrow cells which were cultured for 24 hr with and without erythropoietin. 59Fe‐heme synthesis, [3H]thymidine DNA synthesis, and 14C‐leucine protein synthesis were studied. The results indicated that cultures containing the high mol. wt. pool (>400,000 daltons) had significantly decreased heme, DNA and protein synthesis. This inhibitor also diminished the response to erythropoietin in polycythemic mice. The lower mol. wt. pool stimulated heme synthesis in vitro. To identify the inhibitor further, plasma lipo‐protein classes were isolated by density gradient ultracentrifugation. The very low density lipoprotein (VLDL) and chylomicron fractions markedly inhibited DNA, protein and heme synthesis. Low density and high density lipoprotein fractions were inactive. A lipoprotein inhibitor of erythropoiesis was also identified in cancerous ascitic fluid, and to a lesser degree, in normal rat plasma. We suggest that this VLDL inhibitor of marrow erythropoiesis is a contributing factor in the anaemia of cancer.

Rat Plasma Lipoprotein Inhibitors of Lymphocyte Proliferation: Specific Membrane Receptor for Very Low Density Lipoproteins

“…It was recently demonstrated that phy siologic concentration of normal rat plasma very low density liporoteins (VLDL) mark edly inhibit rat bone marrow cell prolifera tion and mitogen-stimulated spleen lympho cyte DNA synthesis [1]. The potential im mune and hematopoietic role of lipoproteins as probes to understand cell membrane re ceptor physiology, has led to considerable interest in this field.…”