Genetics and metabolic deregulation following cancer initiation: A world to explore

Araldi, Rodrigo Pinheiro; Módolo, Diego Grando; Júnior, Paulo Luiz de Sá; Consonni, Sílvio Roberto; Carvalho, Rogério Falleiros; Roperto, F.; Beçak, Willy; Stocco, Rita de Cássia

doi:10.1016/j.biopha.2016.05.031

Cited by 25 publications

(59 citation statements)

References 136 publications

(280 reference statements)

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“…In this sense, the cell cultures emerges as useful models to study the oxidative stress [5,35]. Thus, this study employed five primary culture: one of BPV-free normal skin (control), one of cutaneous papilloma (papilloma 01), two of fibropapillomas (papilloma 02 and 03) and one of esophageal carcinoma.…”

Section: Cell Culturementioning

confidence: 99%

“…By the contrast, most cancer cells increase the glucose uptake and glycolytic rates even in aerobic conditions, converting the pyruvate to lactate [5,27,30,31]. This metabolic switch, known as "Warburg effect", guarantees the ATP supply to cell proliferation, reducing the ROS levels, which can lead to apoptosis, conferring a protective action to cancer cells [5].…”

Section: Introductionmentioning

confidence: 99%

“…This metabolic switch, known as "Warburg effect", guarantees the ATP supply to cell proliferation, reducing the ROS levels, which can lead to apoptosis, conferring a protective action to cancer cells [5]. Currently studies suggest that the STAT3 nuclear transcription factor is the pivot of metabolic switch verified in transformed cells [32,33].…”

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: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…based on cell culture systems [44], which are mandatory to study the BPV action in cancer progression and metastasis [36]. This occur because, according to the BPV natural history, the viral replication is dependent of cell differentiation [45][46][47].…”

Section: Introductionmentioning

confidence: 99%

“…In equines, BPV is the causative agent of sarcoid, invasiveness but non-metastatic fibroblastic benign neoplasm [32] that affects 11.5% of horses worldwide [33]. Due to the ability to infect different species and in function of morphological and pathogenic similarities with human papillomavirus (HPV), BPV is considered a useful model to study the HPV-associated oncogenic process [8,[34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Bovine papillomavirus productive infection in cell cultures: First evidences

Araldi¹,

Melo²,

Consonni³

et al. 2017

Virol Res Rev

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Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis (BP), infectious disease, characterized by the presence of multiples papillomas that can regress spontaneously or progress to malignances. Although recognized as mutagen, BPV action following cancer initiation remains few explored, since studies about cancer progression and metastasis are based on cell cultures. The lack of attention to in vitro models is a reflection of the papillomavirus replication paradigm, which is dependent of epithelium cell differentiation. Since 2008, we have explored the potential of cell lines derived from BPV-infected neoplasms as model to study the oncogenic process. In this study, we described BPV productive infection in cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma (EC) in which BPV DNA sequences were previously detected by PCR. Considering that the immunodetection of L1 capsid protein is the main evidence of productive infection, we analyzed the expression of this protein by immunofluorescence and flow cytometry. Results showed the immunodetection of L1 protein in cell lines derived from cutaneous papilloma, fibropapilloma and EC, but not in cells derived from BPV-free normal skin. We also observed the presence of spherical and electron-dense particles, with 41.02-61.94 nm diameter in cytoplasmic vesicles of cells in the sixth passage of cutaneous papilloma, fibropapilloma and EC, being compatible with the expected BPV morphology. Cells derived from BPV-free normal skin, in turn, showed membranous particles up to 75.00 nm not compatible with BPV morphology. These results suggest the BPV productive infection in cells lines derived from BPV-infected neoplasm, reinforcing that these cells are useful models to study the viral biology and pathogenesis.Correspondence to: Rita de Cassia Stocco, Genetics Laboratory, Butantan Institute, São Paulo, 05503-900, Brazil, Tel: +55 11 2627-9701; e-mail: rita. stocco@butantan.gov.br Highlights• Bovine papillomavirus (BPV) cause multiples papillomas that can regress or progress to malignances;• BPV action following cancer initiation remains few explored;• Identification of BPV L1 capsid protein and virion-like particles in cytoplasmic vesicles of cell lines derived from BPVinfected cutaneous papilloma, fibropapilloma and esophageal carcinoma;• Cell lines derived from BPV-infected neoplasm can be considered useful model to study the viral biology and pathology.

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Estimating Heritability of Prostate Cancer‐Specific Survival Using Population‐Based Registers

et al. 2017

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Genetics and metabolic deregulation following cancer initiation: A world to explore

Cited by 25 publications

References 136 publications

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

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

Bovine papillomavirus productive infection in cell cultures: First evidences

Estimating Heritability of Prostate Cancer‐Specific Survival Using Population‐Based Registers

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