Metabolic Disorders in Mice Bearing Transplantable Hepatoma 22a: a Focus on Ceruloplasmin

Ceruloplasmin (Cp) plays a key role in the metabolism of two vital trace elements, iron and copper, whose metabolic pathways are closely interconnected and also linked to zinc metabolism. Tumor growth is often accompanied by an increase in blood Cp concentration, but its role in tumor progression remains unclear. The aim of this study was to compare changes in serum Cp concentration with the levels of iron, zinc, pro-inflammatory cytokines, and lipids during tumor growth. Additionally, we investigated the effect of zinc sulfate, administered in drinking water, on Cp levels. The study was carried out on C3HA mice subcutaneously inoculated with hepatoma 22a cells. An increase in Cp began on day 14, coinciding with the emergence of central necroses and elevated circulating triglyceride levels. The rise in blood IL-6 concentration started on day 7 and could serve as a trigger for the acute-phase response development, as manifested by increased Cp synthesis, hypoferremia, hypozincemia, and hypertriglyceridemia. The decrease in non-heme iron levels in the blood and liver occurred later than the Cp increase, suggesting that iron deficiency was not the cause of the elevated Cp concentration on day 14 but might contribute to its maintenance at later stages of hepatoma growth. Zinc sulfate supplementation normalized iron and partially restored zinc levels in the blood of tumor-bearing mice by day 21 but did not affect Cp concentration. The potential pro-tumorigenic role of Cp is discussed, which may be not so much related to its role in iron metabolism as to its ability to transport copper to tissues We hypothesize that serum Cp is an important pathogenetic factor in supplying tumors with essential lipid metabolites, as Cp, together with IL-6, may support lipolysis in adipose tissue by delivering copper ions.