Cancer-related anemia in a rat model: alpha2-macroglobulin from Yoshida sarcoma shortens erythrocyte survival

Implantation of Yoshida ascites sarcoma in rats was found to lead to a reduction in the hemoglobin content, the erythrocyte count and the packed cell volume of blood to 30% of normal in 4 d; however, there was no decrease in the mean cell hemoglobin, the mean cell volume and the mean corpuscular hemoglobin concentration, or suppression of erythropoiesis. The red cells from the circulation of tumor-bearing animals, tagged with (51)Cr and injected intravenously in normal rats, showed significantly faster clearance than normal. The erythrocytes contaminating the tumor ascites exhibited extremely short survival, suggesting that one or more secreted tumor product(s) may be responsible for the effect. Incubation of red cells from normal rats in the cell-free ascites fluid, or with an isoform of alpha2-macroglobulin purified from it, also led to reduction in the survival; but the ascites fluid depleted specifically of alpha2-macroglobulin was without any effect. The erythrocytes exhibiting reduced survival showed a proportionate decrease in their cellular deformability. The study identifies a tumor product that is directly responsible for the causation of anemia in the host, and the mechanism by which it does so.