TY - JOUR

T1 - Tumor- and Fibroblast-Derived Cell-Free DNAs Differently Affect the Progression of B16 Melanoma In Vitro and In Vivo

AU - Filatova, Alina A.

AU - Alekseeva, Ludmila A.

AU - Sen’kova, Aleksandra V.

AU - Savin, Innokenty A.

AU - Sounbuli, Khetam

AU - Zenkova, Marina A.

AU - Mironova, Nadezhda L.

N1 - This research was funded by the Russian Science Foundation (grant no. 22-14-00289) and by the Russian State-funded budget project of ICBFM (grant no. 121031300044-5) (for the use of the equipment).

PY - 2024

Y1 - 2024

N2 - It is widely postulated that the majority of pathologically elevated extracellular or cell-free DNA (cfDNA) in cancer originates from tumor cells; however, evidence has emerged regarding the significant contributions of other cells from the tumor microenvironment. Here, the effect of cfDNA originating from murine B16 melanoma cells and L929 fibroblasts on B16 cells was investigated. It was found that cfDNAL929 increased the viability and migration properties of B16 cells in vitro and their invasiveness in vivo. In contrast, cfDNAB16 exhibited a negative effect on B16 cells, reducing their viability and migration in vitro, which in vivo led to decreased tumor size and metastasis number. It was shown that cell treatment with both cfDNAs resulted in an increase in the expression of genes encoding DNases and the oncogenes Braf, Kras, and Myc. cfDNAL929-treated cells were shown to experience oxidative stress. Gene expression changes in the case of cfDNAB16 treatment are well correlated with the observed decrease in proliferation and migration of B16 cells. The obtained data may indicate the possible involvement of fibroblast DNA in the tumor microenvironment in tumor progression and, potentially, in the formation of new tumor foci due to the transformation of normal cells.

AB - It is widely postulated that the majority of pathologically elevated extracellular or cell-free DNA (cfDNA) in cancer originates from tumor cells; however, evidence has emerged regarding the significant contributions of other cells from the tumor microenvironment. Here, the effect of cfDNA originating from murine B16 melanoma cells and L929 fibroblasts on B16 cells was investigated. It was found that cfDNAL929 increased the viability and migration properties of B16 cells in vitro and their invasiveness in vivo. In contrast, cfDNAB16 exhibited a negative effect on B16 cells, reducing their viability and migration in vitro, which in vivo led to decreased tumor size and metastasis number. It was shown that cell treatment with both cfDNAs resulted in an increase in the expression of genes encoding DNases and the oncogenes Braf, Kras, and Myc. cfDNAL929-treated cells were shown to experience oxidative stress. Gene expression changes in the case of cfDNAB16 treatment are well correlated with the observed decrease in proliferation and migration of B16 cells. The obtained data may indicate the possible involvement of fibroblast DNA in the tumor microenvironment in tumor progression and, potentially, in the formation of new tumor foci due to the transformation of normal cells.

KW - cell-free DNA

KW - fibroblast

KW - melanoma

KW - metastasis

KW - tumor progression

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85194218528&origin=inward&txGid=a25f05d26f4315c7c8f42c9c1435882d

UR - https://www.mendeley.com/catalogue/3f79d6ae-1534-3d60-8425-e1c4439271a7/

U2 - 10.3390/ijms25105304

DO - 10.3390/ijms25105304

M3 - Article

C2 - 38791341

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 10

ER -