Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences (SB RAS), Lavrentiev Ave., 8, Novosibirsk 630090, Russia.
Faculty of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.
Int J Mol Sci. 2024 May 13;25(10):5304. doi: 10.3390/ijms25105304.
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 , , and 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.
人们普遍假设，大多数病理性升高的细胞外或无细胞游离 DNA（cfDNA）来源于肿瘤细胞；然而，已经有证据表明肿瘤微环境中的其他细胞也有重要贡献。在这里，研究了源自鼠 B16 黑色素瘤细胞和 L929 成纤维细胞的 cfDNA 对 B16 细胞的影响。结果发现，cfDNA L929 体外增加了 B16 细胞的活力和迁移特性，体内增加了其侵袭性。相比之下，cfDNA B16 对 B16 细胞表现出负效应，降低了其体外活力和迁移能力，体内导致肿瘤体积减小和转移数量减少。结果表明，cfDNA 处理细胞会导致编码 DNase 和癌基因、和的基因表达增加，cfDNA L929 处理的细胞经历氧化应激。cfDNA B16 处理时的基因表达变化与观察到的 B16 细胞增殖和迁移减少高度相关。获得的数据可能表明，成纤维细胞 DNA 可能参与肿瘤微环境中的肿瘤进展，并可能由于正常细胞的转化而导致新的肿瘤灶形成。
