Abstract
Cell-free DNA is present in different biological fluids and when released by tumor cells may contribute to pro-tumor events such as malignant transformation of cells adjacent to the tumor and metastasis. Thus, this study analyzed the effect of tumor cell-free DNA, isolated from the blood of prostate cancer patients, on non-tumor prostate cell lines (RWPE-1 and PNT-2). To achieve this, we performed cell-free DNA quantification and characterization assays, evaluation of gene and miRNA expression profiling focused on cancer progression and EMT, and metabolomics by mass spectrometry and cellular migration. The results showed that tumor-free cell DNA was able to alter the gene expression of MMP9 and CD44, alter the expression profile of nine miRNAs, and increased the tryptophan consumption and cell migration rates in non-tumor cells. Therefore, tumor cell-free DNA was capable of altering the receptor cell phenotype, triggering events related to malignant transformation in these cells, and can thus be considered a potential target for cancer diagnosis and therapy.
Highlights
Cell-free DNA is present in different biological fluids and when released by tumor cells may contribute to pro-tumor events such as malignant transformation of cells adjacent to the tumor and metastasis
This free circulating DNA has been described as circulating cell-free DNA. cfDNA refers to extracellular DNA fragments that can be detected in different biological fluids[2]
Fragment size and levels of cfDNA were measured in plasma samples from cancer patients (n = 22) and from healthy controls (n = 14)
Summary
Cell-free DNA is present in different biological fluids and when released by tumor cells may contribute to pro-tumor events such as malignant transformation of cells adjacent to the tumor and metastasis. García-Olmo et al.[10], in clinical studies from colon cancer patients, found evidence of gene transfer and cell transformation triggered by nucleic acids isolated from plasma[9,10]. They proposed that plasma cfDNA participates in tumorigenesis and in the development of receptor cell transformation metastases, which they called “genometastasis”[9]. These studies and advances in molecular biology have allowed us to verify the functionality of cfDNA in cellular communication and, in the development and progression of diseases such as cancer[11,12]. Epithelial–mesenchymal transition (EMT) is one of the most discussed biological events in tumorigenesis and metastases, the molecular mechanisms governing EMT and its crosstalk with cfDNA remain poorly understood[13,14]
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