Sarcoid-derived fibroblasts: Links between genomic instability, energy metabolism and senescence

Potocki, Leszek; Lewińska, Anna; Klukowska‐Rötzler, Jolanta; Bielak-Żmijewska, Anna; Grabowska, Wioleta; Rzeszutek, Iwona; Kaminska, Patrycja; Roga, Elzbieta; Bugno‐Poniewierska, Monika; Słota, E.; Mählmann, Kathrin; Koch, Christoph; Wnuk, Maciej

doi:10.1016/j.biochi.2013.10.010

Cited by 19 publications

(18 citation statements)

References 63 publications

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“…In this sense, at the same time that we observed the loss of ΔΨm in fibropapilloma and esophageal carcinoma cells, we verified an increase in MFI, which was confirmed by the Bonferroni's test ( figure 3). These data reinforce the energy compensatory mechanism proposed by Potocki et al [14]. In addition, our data suggest that metabolic alterations are associated to the virus persistence-associated neoplasm progression.…”

Section: Discussionsupporting

confidence: 92%

“…In this sense, the high levels of ROS observed in papilloma and fibropapilloma can be discussed as an additional source of mutations. This because ROS can promote the DNA oxidation, leading to DNA breaks [5] observed in papillomavirus-infected cells lines (table 1, figure 7), as well as those described in literature [10][11][12][13][14]19]. Similar results were also verified in HPV infected cells, in which it was demonstrated that the HPV-16 E6*-induced oxidative stress and DNA breaks, which are necessary to HPV integration [15,16].…”

Section: Discussionsupporting

confidence: 71%

“…Similar results were also described in cell cultures derived from bovines, canines and equines infected with papillomavirus [22]. Currently, Potocki et al [14] reported that sarcoid-derived fibroblast present a loss of mitochondrial membrane potential and changes in energy-supplying pathways in BPV-1-positive cells, which are typical verified in cancer cells. In other study, based on HPV-16, Williams et al [15] demonstrated that E6* oncoprotein, a splicing variant of E6 oncoprotein, promotes the SOD2 and GPx antioxidant enzymes downregulation, resulting in oxidative stress in CaSki and SiHa cells (derived from human cervical carcinoma).…”

Section: Introductionsupporting

confidence: 76%

“…These data suggest that dermal involvement has an important role in pathogenesis of cancer progression. In this sense, Potocki et al [14] demonstrated that BPV-1-positive sarcoid-derivate fibroblasts present a ΔΨm depletion, suggestion that the energy production is compensated by cytosolic glycolysis, suggesting that BPV-mediated metabolic deregulation can lead to "Warburg effect". Depolarization of mitochondrial membrane is common feature of cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, both viruses are associated to benign (warts) and malignant neoplasm. Although it is well stated that both HPV [9] and BPV promote DNA damages (mutations) that can lead to cancer initiation [10][11][12][13], there are few studies about the viral action in cell metabolism [5,[14][15][16]. This occurs due to the lack of attention given to in vitro models [17].…”

Section: Introductionmentioning

confidence: 99%

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Primary Cultures Derived From Bovine Papillomavirus-Infected Lesions As Model To Study Metabolic Deregulation

Stocco¹

2016

Journal of Cancer Research and Therapeutic Oncology

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Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, disease characterized by the presence of multiple papillomas that can regress or to progress to malignances. Due to the pathological similarities with the human papillomavirus (HPV), BPV is considered a prototype to study the papillomavirus-associated oncogenic process. Although it is clear that both BPV and HPV can interact with host chromatin, the interaction of these viruses with cell metabolism remains understudied due to the little attention given to primary cultures derived from papillomavirus-infected lesions. Thus, this study analyzed the energy metabolism, including the mitochondrial membrane potential (ΔΨm) and Reactive Oxygen Species (ROS) of cells derived from cutaneous papilloma, fibropapilloma and Esophageal Carcinoma (EC) as model to evaluate the cell metabolism. These cells were cultivated until sixth passage and subjected to BPV DNA sequences identification by PCR using specific primers to BPV-1, 2 and 4. PCR results showed the presence and maintenance of at least one BPV type along the six passages analyzed. Cells derived from normal skin, without BPV DNA sequences were used as control. Results of energy metabolism showed the loss of ΔΨm in fibropapilloma and EC cells, suggesting a metabolic switch compatible to the activation of aerobic glycolysis. Cutaneous papilloma and normal skin cells showed the maintenance of ΔΨm. Paradoxically, cutaneous papilloma and fibropapilloma presented high levels of ROS production, while the EC cells reduced the ROS levels, reinforcing the activation of glycolytic metabolism. Our results suggest that the metabolic switch is mediated by BPV E6 oncoprotein, since the addition of this oncoprotein in normal cells promoted the oxidative stress. The oxidative stress showed able to activate the STAT3 nuclear factor in papilloma and fibropapilloma cells, contributing to metabolic deregulation. These data suggest that primary cultures are useful model to study the interaction between BPV and cell metabolism.

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Section: Discussionsupporting

confidence: 92%