ArticlePloS one2015
Cell Free DNA of Tumor Origin Induces a 'Metastatic' Expression Profile in HT-29 Cancer Cell Line.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Circulating Nucleic Acids in Maternal Plasma and Serum in Pregnancy Complications: Are They Really Useful in Clinical Practice? A Systematic Review.Molecular diagnosis & therapy · 2020Pooled it
- Cell-Free DNA (cfDNA), Its Applications in Cancer Diagnosis and Monitoring, and Its Potential Role in Regulating Cancer Metabolism.Advances in experimental medicine and biology · 2026Review
- Anti-cancer Potential of Scopoletin Derivatives Across Diverse Cancer Cell Lines: A Comprehensive Review.Current drug discovery technologies · 2026Review
- GC-Reach DNA Fragments Reduce the Expression of Survival Genes in MCF7 Breast Carcinoma Cells: TLR9/MyD88/NF-κB Signaling Pathway as a Potential Target for Cancer Therapy.Bulletin of experimental biology and medicine · 2025Article
- TLR9: A Double-Dealing Toll-Like Receptor.ImmunoTargets and therapy · 2025Review
- Regulation of term and preterm labor: genetics and epigenetics.Frontiers in genetics · 2025Article
- Review
- Cell-free DNA in the management of prostate cancer: Current status and future prospective.Asian journal of urology · 2023Review
- Non-Targeted Serum Lipidomics Analysis and Potential Biomarkers of Laryngeal Cancer Based on UHPLC-QTOF-MS.Metabolites · 2022Article
- The Overview of Perspectives of Clinical Application of Liquid Biopsy in Non-Small-Cell Lung Cancer.Life (Basel, Switzerland) · 2022Review
- New Perspectives on the Importance of Cell-Free DNA Biology.Diagnostics (Basel, Switzerland) · 2022Review
- Metallothionein 2A (MT2A) controls cell proliferation and liver metastasis by controlling the MST1/LATS2/YAP1 signaling pathway in colorectal cancer.Cancer cell international · 2022Article
- Drug delivery carriers with therapeutic functions.Advanced drug delivery reviews · 2021Review
- LIPG: an inflammation and cancer modulator.Cancer gene therapy · 2021Review
- Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer.Cancers · 2020Article
- Tumor microenvironment complexity and therapeutic implications at a glance.Cell communication and signaling : CCS · 2020Review
- Inflammation-mediated generation and inflammatory potential of human placental cell-free fetal DNA.Placenta · 2020Article
- The emerging role of cell-free DNA as a molecular marker for cancer management.Biomolecular detection and quantification · 2019Review
- LncRNA-MALAT1 regulates proliferation and apoptosis of ovarian cancer cells by targeting miR-503-5p.OncoTargets and therapy · 2019Article
- Life and death of circulating cell-free DNA.Cancer biology & therapy · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpithelial cells in malignant conditions release DNA into the extracellular compartment. Cell free DNA of tumor origin may act as a ligand of DNA sensing mechanisms and mediate changes in epithelial-stromal interactions.
aimsTo evaluate and compare the potential autocrine and paracrine regulatory effect of normal and malignant epithelial cell-related DNA on TLR9 and STING mediated pathways in HT-29 human colorectal adenocarcinoma cells and normal fibroblasts. MATERIALS AND
methodsDNA isolated from normal and tumorous colonic epithelia of fresh frozen surgically removed tissue samples was used for 24 and 6 hour treatment of HT-29 colon carcinoma and HDF-α fibroblast cells. Whole genome mRNA expression analysis and qRT-PCR was performed for the elements/members of TLR9 signaling pathway. Immunocytochemistry was performed for epithelial markers (i.e. CK20 and E-cadherin), DNA methyltransferase 3a (DNMT3a) and NFκB (for treated HDFα cells).
resultsAdministration of tumor derived DNA on HT29 cells resulted in significant (p<0.05) mRNA level alteration in 118 genes (logFc≥1, p≤0.05), including overexpression of metallothionein genes (i.e. MT1H, MT1X, MT1P2, MT2A), metastasis-associated genes (i.e. TACSTD2, MACC1, MALAT1), tumor biomarker (CEACAM5), metabolic genes (i.e. INSIG1, LIPG), messenger molecule genes (i.e. DAPP, CREB3L2). Increased protein levels of CK20, E-cadherin, and DNMT3a was observed after tumor DNA treatment in HT-29 cells. Healthy DNA treatment affected mRNA expression of 613 genes (logFc≥1, p≤0.05), including increased expression of key adaptor molecules of TLR9 pathway (e.g. MYD88, IRAK2, NFκB, IL8, IL-1β), STING pathway (ADAR, IRF7, CXCL10, CASP1) and the FGF2 gene.
conclusionsDNA from tumorous colon epithelium, but not from the normal epithelial cells acts as a pro-metastatic factor to HT-29 cells through the overexpression of pro-metastatic genes through TLR9/MYD88 independent pathway. In contrast, DNA derived from healthy colonic epithelium induced TLR9 and STING signaling pathway in normal fibroblasts.
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Registered trials
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