Sarcoid-derived fibroblasts: links between genomic instability, energy metabolism and senescence.
Abstract: Bovine papillomavirus 1 (BPV-1) is a well recognized etiopathogenetic factor in a cancer-like state in horses, namely equine sarcoid disease. Nevertheless, little is known about BPV-1-mediated cell transforming effects. It was shown that BPV-1 triggers genomic instability through DNA hypomethylation and oxidative stress. In the present study, we further characterized BPV-1-positive fibroblasts derived from sarcoid tumors. The focus was on cancer-like features of sarcoid-derived fibroblasts, including cell cycle perturbation, comprehensive DNA damage analysis, end-replication problem, energy metabolism and oncogene-induced premature senescence. The S phase of the cell cycle, polyploidy events, DNA double strand breaks (DSBs) and DNA single strand breaks (SSBs) were increased in BPV-1-positive cells compared to control fibroblasts. BPV-1-mediated oxidative stress may contribute to telomere dysfunction in sarcoid-derived fibroblasts. Loss of mitochondrial membrane potential and concurrent elevation in intracellular ATP production may be a consequence of changes in energy-supplying pathways in BPV-1-positive cells which is also typical for cancer cells. Shifts in energy metabolism may support rapid proliferation in cells infected by BPV-1. Nevertheless, sarcoid-derived fibroblasts representing a heterogeneous cell fraction vary in some aspects of metabolic phenotype due to a dual role of BPV-1 in cell transformation and oncogene-induced premature senescence. This was shown with increased senescence-associated β-galactosidase (SA-β-gal) activity. Taken together, metabolic phenotypes in sarcoid-derived fibroblasts are plastic, which are similar to greater plasticity of cancer tissues than normal tissues.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Publication Date: 2013-10-19 PubMed ID: 24148276DOI: 10.1016/j.biochi.2013.10.010Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates how Bovine papillomavirus 1 (BPV-1) triggers cancer-like conditions, specifically equine sarcoid disease in horses. It examines the damage BPV-1 infection does to horse cell DNA and how BPV-1 causes genomic instability, cellular energy changes, and premature aging in the cells.
Genomic Instability by BPV-1
- Bovine papillomavirus 1 (BPV-1) is confirmed as a major factor causing equine sarcoid disease, a cancer-like state in horses.
- BPV-1 has been shown to trigger genetic instability in horse cells through DNA hypomethylation and oxidative stress.
BPV-1 Effects on Cell Cycle
- The research focused on the impact of BPV-1 on fibroblasts, a type of horse cell derived from the sarcoid tumors.
- In cells infected with BPV-1, abnormalities in the cell cycle were observed. There were increased events of multiple copies of the genome within a cell (polyploidy events), and more DNA damage in the form of DNA double strand breaks (DSBs) and DNA single strand breaks (SSBs).
Energy Metabolism and BPV-1
- The oxidative stress caused by BPV-1 might contribute to a malfunction in the ends of the chromosomes (telomere dysfunction) in sarcoid-derived fibroblasts.
- Energy changes were also observed in the form of loss of mitochondrial membrane potential and a concurrent increase in intracellular ATP production. This suggests that BPV-1 may alter energy-supplying pathway in cells, an attribute commonly seen in cancer cells.
- Shifts in energy metabolism could support rapid cell proliferation during BPV-1 infection, leading to the rapid growth and spread of the disease.
Impact on Cell Senescence
- BPV-1 appears to have a dual role in the transformation of cells and premature senescence. This is observed through the increased activity of senescence-associated β-galactosidase (SA-β-gal), an enzyme linked to cellular aging.
- The fibroblasts derived from sarcoids demonstrated diversity in metabolic phenotype, showing that BPV-1 has varying impacts on different cells.
- The metabolic characteristics of these fibroblasts were observed to be plastic, mirroring the high adaptability and diversity often seen in cancer tissues compared to normal tissues.
Cite This Article
APA
Potocki L, Lewinska A, Klukowska-Rötzler J, Bielak-Zmijewska A, Grabowska W, Rzeszutek I, Kaminska P, Roga E, Bugno-Poniewierska M, Slota E, Mählmann K, Koch C, Wnuk M.
(2013).
Sarcoid-derived fibroblasts: links between genomic instability, energy metabolism and senescence.
Biochimie, 97, 163-172.
https://doi.org/10.1016/j.biochi.2013.10.010 Publication
Researcher Affiliations
- Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
- Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland; Department of Biochemistry and Cell Biology, University of Rzeszow, Poland.
- Division of Pedriatric Hematology/Oncology, Department of Clinical Research, University of Bern, Switzerland.
- Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
- Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
- Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
- Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
- Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
- Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland; Laboratory of Genomics, National Research Institute of Animal Production, Balice n. Cracow, Poland.
- Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
- ISME - Equine Clinic Bern, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Switzerland.
- ISME - Equine Clinic Bern, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Switzerland.
- Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland. Electronic address: mawnuk@gmail.com.
MeSH Terms
- Animals
- Bovine papillomavirus 1
- Cell Cycle
- Cell Transformation, Neoplastic / genetics
- Cell Transformation, Neoplastic / metabolism
- Cell Transformation, Neoplastic / pathology
- Cellular Senescence
- DNA Breaks, Double-Stranded
- DNA Breaks, Single-Stranded
- DNA, Viral / genetics
- Energy Metabolism
- Fibroblasts / metabolism
- Fibroblasts / pathology
- Fibroblasts / virology
- Gene Expression
- Genomic Instability
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horse Diseases / virology
- Horses
- Oxidative Stress
- Papillomavirus Infections / metabolism
- Papillomavirus Infections / pathology
- Papillomavirus Infections / veterinary
- Papillomavirus Infections / virology
- Ploidies
- Skin Neoplasms / metabolism
- Skin Neoplasms / pathology
- Skin Neoplasms / veterinary
- Skin Neoplasms / virology
- beta-Galactosidase / genetics
- beta-Galactosidase / metabolism
Citations
This article has been cited 4 times.- Rybaczek D, Musiałek MW, Vrána J, Petrovská B, Pikus EG, Doležel J. Kinetics of DNA Repair in Vicia faba Meristem Regeneration Following Replication Stress. Cells 2021 Jan 7;10(1).
- Martano M, Power K, Restucci B, Pagano I, Altamura G, Borzacchiello G, Maiolino P. Expression of vascular endothelial growth factor (VEGF) in equine sarcoid. BMC Vet Res 2018 Sep 3;14(1):266.
- Araldi RP, Assaf SMR, Carvalho RF, Carvalho MACR, Souza JM, Magnelli RF, Módolo DG, Roperto FP, Stocco RC, Beçak W. Papillomaviruses: a systematic review. Genet Mol Biol 2017 Jan-Mar;40(1):1-21.
- Rybaczek D, Musiałek MW, Balcerczyk A. Caffeine-Induced Premature Chromosome Condensation Results in the Apoptosis-Like Programmed Cell Death in Root Meristems of Vicia faba. PLoS One 2015;10(11):e0142307.
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