Functionality of CNAPS in Cancer: The Theory of Genometastasis

García‐Olmo, Dolores C.; Guadalajara, Héctor; Domínguez-Berzosa, Carolina; Picazo, María G.; García-Arranz, Mariano; Garcı́a-Olmo, Damián

doi:10.1007/978-90-481-9382-0_15

Cited by 8 publications

(10 citation statements)

References 15 publications

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“…It is presumed that circulating DNA is derived from DNA released from tumor cells from the site of disease activity 120 . It is reasonable to speculate that in systemic diseases such as diabetes, CKD and atherosclerosis DNA derived from PBMC could be used as a viable surrogate for localized organ specific diseases 78;80;96;121 .…”

Section: Perspective On Epigenetic Research In Nephrologymentioning

confidence: 99%

Beyond genetics: epigenetic code in chronic kidney disease

Dwivedi

Herman

McCaffrey

et al. 2011

Kidney International

116

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Epigenetics refers to a heritable change in the pattern of gene expression that is mediated by a mechanism specifically not due to alterations in the primary nucleotide sequence. Well known epigenetic mechanisms encompass DNA methylation, chromatin remodeling (histone modifications) and RNA interference. Functionally, epigenetics provides an extra layer of transcriptional control and plays a crucial role in normal physiological development, as well as in pathological conditions. Aberrant DNA methylation is implicated in immune dysfunction, inflammation and insulin resistance. Epigenetic changes may be responsible for “metabolic memory” and development of micro- and macrovascular complications of diabetes. MicroRNAs are critical in the maintenance of glomerular homeostasis and hence RNA interference may be important in the progression of renal disease. Recent studies have shown that epigenetic modifications orchestrate the epithelial-mesenchymal transition and eventually fibrosis of the renal tissue. Oxidative stress, inflammation, hyperhomocysteinemia and uremic toxins could induce epimutations in chronic kidney disease. Epigenetic alterations are associated with inflammation and cardiovascular disease in patients with chronic kidney disease. Reversible nature of the epigenetic changes gives an unique opportunity to halt or even reverse the disease process through targeted therapeutic strategies.

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Section: Perspective On Epigenetic Research In Nephrologymentioning

confidence: 99%

Beyond genetics: epigenetic code in chronic kidney disease

Dwivedi

Herman

McCaffrey

et al. 2011

Kidney International

116

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“…Other potentially detrimental functions implicated for cf-DNA include the horizontal transfer of oncogenic sequences (i.e. genometastasis) [8] and the creation of a proinflammatory milieu in the circulation [9]. Endogenous or microbial DNA are also known to act as alerting signals to the host immune system, and various soluble, membrane-bound and intracellular receptors that can recognise DNA have been identified.…”

Section: Introductionmentioning

confidence: 99%

A Genome-Wide Association Study Identifies UGT1A1 as a Regulator of Serum Cell-Free DNA in Young Adults: The Cardiovascular Risk in Young Finns Study

et al. 2012

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Introduction Circulating cell-free DNA (cf-DNA) is a useful indicator of cell death, and it can also be used to predict outcomes in various clinical disorders. Several innate immune mechanisms are known to be involved in eliminating DNA and chromatin-related material as part of the inhibition of potentially harmful autoimmune responses. However, the exact molecular mechanism underlying the clearance of circulating cf-DNA is currently unclear. Methods To examine the mechanisms controlling serum levels of cf-DNA, we carried out a genome-wide association analysis (GWA) in a cohort of young adults (aged 24–39 years; n = 1841; 1018 women and 823 men) participating in the Cardiovascular Risk in Young Finns Study. Genotyping was performed with a custom-built Illumina Human 670 k BeadChip. The Quant-iT TM high sensitivity DNA assay was used to measure cf-DNA directly from serum. Results The results revealed that 110 single nucleotide polymorphisms (SNPs) were associated with serum cf-DNA with genome-wide significance (p<5×10 −8 ). All of these significant SNPs were localised to chromosome 2q37, near the UDP-glucuronosyltransferase 1 (UGT1) family locus, and the most significant SNPs localised within the UGT1 polypeptide A1 ( UGT1A1 ) gene region. Conclusion The UGT1A1 enzyme catalyses the detoxification of several drugs and the turnover of many xenobiotic and endogenous compounds by glucuronidating its substrates. These data indicate that UGT1A1-associated processes are also involved in the regulation of serum cf-DNA concentrations.

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“…These factors permit lateral or horizontal transfer of oncogenic traits to target susceptible cells by activating survival and mitogenic signals [18][19][20]29,34,35]. Pioneering work termed this mode of oncogenic traits transfer "genometastasis" [6,36] as opposed to the classical seed and soil theory of metastasis [2][3][4][5]. The proof of principle of the genometastasis theory has been reported earlier by different groups using an immortalized mouse fibroblast cell line (i.e.…”

Section: Discussionmentioning

confidence: 99%

Transfer of malignant trait to immortalized human cells following exposure to human cancer serum

Abdouh

Zhou

Arena

et al. 2014

J Exp Clin Cancer Res

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Background: Human cancer cells can transfer signaling molecules to neighboring and distant cells predisposing them to malignant transformation. This process might contribute to tumor progression and invasion through delivery of oncogenes or inhibitors of tumor suppressor genes, derived from the primary tumor cells, to susceptible target cells. The oncogenic potential of human cancer serum has been described in immortalized mouse fibroblasts but has not been shown yet in human cells. The objective of this study was to determine whether metastatic cancer patient sera have the ability to induce neoplastic transformation in immortalized human embryonic kidney (HEK293) cells, human embryonic stem cells (hESCs), human mesenchymal stem cells (hMSCs) and human adult liver fibroblasts (hALFs). Methods: Early passage HEK293 cells, hESCs, hMSCs and hALFs were exposed to cancer patient serum, or cancer cells-derived condition medium for 3 weeks. Treated cells were analyzed for cell proliferation and transformation both in vitro and in vivo. Results: HEK293 cells exposed to cancer serum increased their proliferative capability and displayed characteristics of transformed cells, as evaluated by in vitro anchorage-independent growth assay and in vivo tumorigenesis in immunodeficient mice. The same phenotypes were acquired when these cells were cultured in cancer cell line conditioned medium suggesting that the putative oncogenic factors present in the serum might derive directly from the primary tumor. Histopathological analyses revealed that the tumors arising from cancer patient serum and conditioned medium-treated HEK293 cells were poorly differentiated and displayed a high proliferative index. In contrast, neither of these phenomena was observed in treated hMSCs and hALFs. Intriguingly enough, hESC-treated cells maintained their self-renewal and differentiation potentials, as shown by in vitro sphere formation assay and in vivo development of teratomas in immunodeficient mice. Conclusion: Our results indicate that cancer patients serum is able to induce oncogenic transformation of HEK293 cells and maintain the self-renewal of hESCs. To our knowledge, this is the first study that demonstrates the oncogenic transformation potential of cancer patient serum on human cells. In depth characterization of this process and the molecular pathways involved are needed to confirm its validity and determine its potential use in cancer therapy.

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Functionality of CNAPS in Cancer: The Theory of Genometastasis

Cited by 8 publications

References 15 publications

Beyond genetics: epigenetic code in chronic kidney disease

Beyond genetics: epigenetic code in chronic kidney disease

A Genome-Wide Association Study Identifies UGT1A1 as a Regulator of Serum Cell-Free DNA in Young Adults: The Cardiovascular Risk in Young Finns Study

Transfer of malignant trait to immortalized human cells following exposure to human cancer serum

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