Impact of cell-free dna from blood serum of mice with metastatic melanoma on the enhancement of oncogenic properties of melanoma cells

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Abstract

Currently, a significant increase in the levels of circulating cell-free DNA (cfDNA) in the blood of patients is a generally recognized marker of the development of oncological diseases. Although tumor-associated cfDNA has been well studied, its biological functions remain unclear. In this work, we investigated the effect of cfDNA isolated from the blood serum of mice with B16-F10 metastatic melanoma on the properties of B16-F10 melanoma cells in vitro. It was found that the profile of cfDNA isolated form blood serum of mice with melanoma differs significantly from the cfDNA isolated from blood serum of healthy mice, and is similar concerning the abundance of oncogenes and mobile genetic elements (MGE) to the genomic DNA of B16 cells. It was shown that cfDNA of mice with melanoma penetrated into B16 cells, resulting to the increase in the abundance of oncogenes and MGE fragments, and caused the 5-fold increased mRNA level of the secreted DNase Dnase1l3 and a slight increase of the mRNA level of the Jun, Fos, Ras, and Myc oncogenes. cfDNA of healthy mice caused increasing of mRNA level of the intracellular regulatory DNase EndoG and a 4-fold increase of mRNA level of Fos and Ras oncogenes, which are well-known triggers of a large number of signal cascades, from apoptosis inhibition to increased tumor cell proliferation. Thus, it is obvious that the circulating cfDNA of tumor origin is able to penetrate into cells and, despite the fact that no changes were found in the level of viability and migration activity of tumor cells, cfDNA, even with a single exposure, can cause changes at the cellular level that increase the oncogenicity of recipient cells.

About the authors

A. A Filatova

Institute of Chemical Biology and Fundamental Medicine, Siberiab Branch of Russian Academy of Sciences;Faculty of Natural Sciences, Novosibirsk State University

630090 Novosibirsk, Russia;630090 Novosibirsk, Russia

L. A Alekseeva

Institute of Chemical Biology and Fundamental Medicine, Siberiab Branch of Russian Academy of Sciences

630090 Novosibirsk, Russia

I. A Savin

Institute of Chemical Biology and Fundamental Medicine, Siberiab Branch of Russian Academy of Sciences

630090 Novosibirsk, Russia

A. V Sen'kova

Institute of Chemical Biology and Fundamental Medicine, Siberiab Branch of Russian Academy of Sciences

630090 Novosibirsk, Russia

M. A Zenkova

Institute of Chemical Biology and Fundamental Medicine, Siberiab Branch of Russian Academy of Sciences

630090 Novosibirsk, Russia

N. L Mironova

Institute of Chemical Biology and Fundamental Medicine, Siberiab Branch of Russian Academy of Sciences

Email: mironova@niboch.nsc.ru
630090 Novosibirsk, Russia

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