Metabolic alterations in mice bearing hepatoma 22A: focus on ceruloplasmin

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Abstract

Ceruloplasmin (Cp), plays a key role in metabolism of two vital trace elements – iron and copper, whose metabolic pathways are closely related to each other as well as to zinc uptake. Increased concentration of Cp usually follows tumor growth, but its role in tumor progression is not clear. The aim of the study was to compare the changes of Cp concentration in blood serum with iron and zinc content as well as with concentrations of proinflammatory cytokines and lipids in the dynamics of tumor growth. Additionally, Cp concentration was studied in mice supplemented with zinc sulphate in drinking water. The study was performed in C3HA mice, which were subcutaneously inoculated with hepatoma 22a cells. Serum Cp increased from 14th day after tumor inoculation simultaneously with the appearence of central necrosis in the tumor and elevation of serum triglycerides. The growth of blood IL-6 concentration began from 7th day and could possibly trigger the acute phase reaction expressed in increase in Cp synthesis and the development of hypoferremia, hypozincemia and hypertriglyceridemia. The content of non-heme iron in blood and liver decreased later than Cp up-regulation. This indicates that iron deficiency was not the cause of Cp increase on 14th day, but could support it at later stages of tumor growth. Zinc sulphate supplementation returned non-heme iron content and partly returned zinc concentration in the blood of mice on 21st day, but did not influence the concentration of Cp. It is discussed that the possible protumoral role of Cp is related not as much to iron metabolism as to its ability to transport copper to tissues. We hypothesize that serum Cp is an important pathogenetic factor that participates in supplementation of tumors with necessary lipid metabolites since Cp, together with IL-6, can possibly support lipolysis in adipose tissue, delivering copper ions there.

About the authors

E. A. Zelenskyi

Institute of Experimental Medicine

Email: ekissele@yandex.ru
Saint Petersburg, Russia;

K. V. Rutto

St. Petersburg State Technological Institute (Technical University)

Saint Petersburg, Russia

A. S. Trulioff

Institute of Experimental Medicine

Saint Petersburg, Russia

N. P. Gorbunov

Saint Petersburg Pasteur Institute

Saint Petersburg, Russia

A. V. Sokolov

Smorodintsev Research Institute of Influenza

Saint Petersburg, Russia

E. P. Kisseleva

Institute of Experimental Medicine

Saint Petersburg, Russia

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