Role of Cell-Free DNA and Deoxyribonucleases in Tumor Progression

Abstract

Many studies have reported an increase in the level of circulating cell-free DNA (cfDNA) in the blood of patients with cancer. cfDNA mainly comes from tumor cells and, therefore, carries features of its genomic profile. Moreover, tumor-derived cfDNA can act like oncoviruses, entering the cells of vulnerable organs, transforming them and forming metastatic nodes. Another source of cfDNA is immune cells, including neutrophils that generate neutrophil extracellular traps (NETs). Despite the potential eliminative effect of NETs on tumors, in some cases, their excessive generation provokes tumor growth as well as invasion. Considering both possible pathological contributions of cfDNA, as an agent of oncotransformation and the main component of NETs, the study of deoxyribonucleases (DNases) as anticancer and antimetastatic agents is important and promising. This review considers the pathological role of cfDNA in cancer development and the role of DNases as agents to prevent and/or prohibit tumor progression and the development of metastases.

Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies

“…According to his approach, the replacement of apoptosis-activated endogenous DNAses with human recombinant DNAse I might help to bypass cancer defense mechanisms, increasing the killing efficiency of chemo and radiotherapy-resistant tumor cells ( 268 ). Since the inactivation of endogenous DNAse X gene was found in many tumor cells types, the strategies to restore the levels of DNAse X in cancer cells could be an important targeted therapy ( 267 , 269 ). Delivery of vectors encoding several DNAses under one common promoter into the cancer cells could successfully induce apoptosis ( 268 , 269 ).…”

“…Since the inactivation of endogenous DNAse X gene was found in many tumor cells types, the strategies to restore the levels of DNAse X in cancer cells could be an important targeted therapy ( 267 , 269 ). Delivery of vectors encoding several DNAses under one common promoter into the cancer cells could successfully induce apoptosis ( 268 , 269 ).…”

Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer

“…There is evidence for the presence of horizontal (cell-to-cell) DNA transfer not only in bacteria, but in mammals as well [ 95 ]. The large quantity of tumor-derived cfDNAs in the blood of cancer patients suggests their possible function as carriers of certain “tumorigenic” properties to normal cells [ 96 ], supported by the observation that the concentration of cfDNA is five times higher in CRC cases than in healthy individuals [ 69 ]. The term “genometastasis” is now used by some authors after some successful experiments on malignized normal cells with tumor-derived cfDNA, such as the transfer of the tumor specific KRAS mutation by adding the serum of a CRC patient to a healthy cell line [ 97 ].…”

Serum cell‐free DNA as a new biomarker in cutaneous T‐cell lymphoma

“…These results indicate the possibility that extracellular DNA released from tumor or non-tumor cells may in turn affect the pathological development of CTCL. 33 The biological role of extracellular DNA in cancer development is still less understood. Extracellular DNA, by itself or in combination with a certain kind of proteins and lipoproteins, triggers biological responses associated with cancer development.…”

“…Extracellular DNA, by itself or in combination with a certain kind of proteins and lipoproteins, triggers biological responses associated with cancer development. 33 It is reported that pro-metastatic genes are induced through TLR9/Myd88 independent pathway by tumor-derived DNA in colon cancer cell lines. 34 Considering that the elevation of cfDNA levels is associated with poor prognosis, extracellular DNA released from CTCL patients may accelerate the disease progression through a positive feedforward loop.…”