Cell-free and cell-bound circulating nucleic acid complexes: mechanisms of generation, concentration and content

Rykova, Elena Y.; Morozkin, Evgeny S.; Ponomaryova, Anastasia A.; Loseva, Ekaterina M; Zaporozhchenko, Ivan A.; Чердынцева, Н. В.; Vlassov, Valentin V.; Laktionov, Pavel P.

doi:10.1517/14712598.2012.673577

Cited by 87 publications

(73 citation statements)

References 72 publications

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“…Furthermore, eRNA is associated with microparticles (33), which was confirmed by recent experiments. Alternatively, binding to tumor cells might increase the stability and half-life of extracellular ribonucleic acids in vivo (34,35). Together, there is no doubt Figure 5.…”

Section: Discussionmentioning

confidence: 99%

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Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression

et al. 2013

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Extracellular RNA (eRNA) released from injured cells promotes tissue permeability, thrombosis, and inflammation in vitro and in vivo, and RNase1 pretreatment can reduce all these effects. In this study, we investigated the role of the eRNA/RNase1 system in tumor progression and metastasis. Under quiescent and stimulatory conditions, tumor cells released much higher levels of endogenous extracellular RNA (eRNA) than nontumor cells. In glioblastomas, eRNA was detected at higher levels in tumors than nontumor tissue. eRNA induced tumor cells to adhere to and migrate through human cerebral microvascular endothelial cells (HCMEC/D3), in a manner requiring activation of VEGF signaling. In addition, eRNA liberated TNF-a from macrophages in a manner requiring activation of the TNF-a-converting enzyme TACE. Accordingly, supernatants derived from eRNAtreated macrophages enhanced tumor cell adhesion to HCMEC/D3. TNF-a release evoked by eRNA relied upon signaling activation of mitogen-activated protein kinases and the NF-kB pathway. In subcutaneous xenograft models of human cancer, administration of RNase1 but not DNase decreased tumor volume and weight. Taken together, these results suggest that eRNA released from tumor cells has the capacity to promote tumor cell invasion through endothelial barriers by both direct and indirect mechanisms, including through a mechanism involving TNF-a release from tumor-infiltrating monocytes/macrophages. Our findings establish a crucial role for eRNA in driving tumor progression, and they suggest applications for extracellular RNase1 as an antiinvasive regimen for cancer treatment. Cancer Res; 73(16); 5080-9. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, eRNA itself seems to be involved in tumor cell binding to endothelial cells, as cancer cell adhesion was prevented by RNase1. Whether cell-bound RNA (34,35) itself could strengthen cellular contacts in this regard requires further studies.…”

Section: Discussionmentioning

confidence: 99%

Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression

et al. 2013

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“…Dying cells release DNA into the bloodstream contributing to the pool of circulating cfDNA (1)(2)(3)(4)(5)(6)(7)(8)(9). cfDNA is an active biological agent.…”

Section: Discussionmentioning

confidence: 99%

“…There are several hypotheses concerning the origin of cfDNA, including the cell death hypothesis and the hypothesis that living cells actively secrete DNA as signaling molecules. CfDNA is a potential marker for pathological processes and is of importance for diagnostic purposes (1)(2)(3)(4)(5)(6)(7)(8)(9). cfDNA in a fetus was first reported to be present in maternal blood in 1997, when Lo et al (10) demonstrated that maternal plasma contains Y-chromosomal sequence of the male fetus.…”

Section: Introductionmentioning

confidence: 99%

Circulating cell-free DNA concentration and DNase I activity of peripheral blood plasma change in case of pregnancy with intrauterine growth restriction compared to normal pregnancy

et al. 2017

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Abstract. The level of apoptosis is increased during pregnancy. Dying cells emit DNA that remains in blood circulation and is known as cell-free DNA (cfDNA). The concentration of cfDNA can reflect the level of cell death. The present article is the result of studying cfDNA concentration and DNase I activity in the blood plasma of 40 non-pregnant women (control), 40 healthy pregnant women (over 37 weeks) and 40 pregnant women with a diagnosis of intrauterine growth restriction (IUGR). In order to explain the obtained results, a program modeling the change of cfDNA concentration under the influence of different internal and external factors was written. It was reported that, despite the fact that the level of cell death is increased, cfDNA concentration in blood can be decreased due to activation of cfDNA elimination system. A significant increase of DNase I activity has been reported in cases of IUGR. Increase in DNase I activity over a certain threshold indicates presence of pathological processes in the organism. CfDNA circulating in blood cannot be a reliable marker of increased cell death during pregnancy. Thus, assessment of the level of cell death during pregnancy should be done by simultaneous analysis of cfDNA level and DNase I activity.

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“…In this sense, they suggest that such a nucleosome footprint could be applied to infer tissue origin of the ccfDNA [33]. In summary, there are two overwhelming functional aspects of ccfDNA, the capacity to behave as an intercellular messenger and the genometastasis [26] [27].…”

Section: Circulating Cell Free Dna (Ccfdna)mentioning

confidence: 99%

Liquid Biopsy in Liquid Tumors

Ranuncolo¹

2017

JCT

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The availability of a minimally invasive patient simple, capable of providing tumor information, represents a valuable clinical tool. The liquid biopsy has the potential to achieve this need. Circulating cell free DNA (ccfDNA), other circulating nucleic acids such as microRNA and circulating tumor cells (CTCs), can be obtained from a peripheral blood sample. Liquid biopsy has been particularly studied in solid tumors, specially of the epitelial origin, such as a pancreatic carcinoma and advanced breast cancer. It has been considerably less applied to the study of non-solid tumors. It represents an important source for diagnosis, prognosis and predictive information. Also it is suitable to evaluate response to therapy and drugs pharmacokinetics. It provides a unique opportunity to evaluate the disease evolution in serial blood samples collection, otherwise difficult to obtain. Liquid biopsy can be rehearsed using different circulating biological fluids such as whole blood, serum, plasma and lymph, as well as, non-circulating fluids such as urine, feces, saliva, bile and accumulated pathological fluids such as ascites. This review summarizes the current status of circulating material analysis in non-solid tunors. It is specially focused on Hodgkin Lymphoma and among Non-Hodgkin Lymphoma, it refers particularly to Diffuse Large B cell Lymphoma, the most common aggressive Non-Hodgkin Lymphoma derived from germinal center B-cells in adults. It further discusses the benefit of liquid biopsy in oncohemtaological diseases and potential clinical applications.

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Cell-free and cell-bound circulating nucleic acid complexes: mechanisms of generation, concentration and content

Cited by 87 publications

References 72 publications

Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression

Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression

Circulating cell-free DNA concentration and DNase I activity of peripheral blood plasma change in case of pregnancy with intrauterine growth restriction compared to normal pregnancy

Liquid Biopsy in Liquid Tumors

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