title: 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.
authors.affiliation: Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Potocki
authors.affiliation: Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland; Department of Biochemistry and Cell Biology, University of Rzeszow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lewinska
authors.affiliation: Division of Pedriatric Hematology/Oncology, Department of Clinical Research, University of Bern, Switzerland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Klukowska-Rötzler
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bielak-Zmijewska
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
authors.forename: Wioleta
authors.initials: W
authors.lastname: Grabowska
authors.affiliation: Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Rzeszutek
authors.affiliation: Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Kaminska
authors.affiliation: Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Roga
authors.affiliation: 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.
authors.forename: Monika
authors.initials: M
authors.lastname: Bugno-Poniewierska
authors.affiliation: Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Kolbuszowa, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Slota
authors.affiliation: ISME - Equine Clinic Bern, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Mählmann
authors.affiliation: ISME - Equine Clinic Bern, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Koch
authors.affiliation: 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.
authors.forename: Maciej
authors.initials: M
authors.lastname: Wnuk
mesh_terms: D000818:Animals; D052688:Bovine papillomavirus 1; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016922:Cellular Senescence; D053903:DNA Breaks, Double-Stranded; D053904:DNA Breaks, Single-Stranded; D004279:DNA, Viral / Q000235:genetics; D004734:Energy Metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015870:Gene Expression; D042822:Genomic Instability; D006734:Horse Diseases / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D006736:Horses; D018384:Oxidative Stress; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D011003:Ploidies; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D001616:beta-Galactosidase
keywords: ATP; BPV-1; Cell cycle; Equine; Genomic instability; SA-β-gal; Sarcoid-derived fibroblasts