Deoxynivalenol induces structural alterations in epidermoid carcinoma cells A431 and impairs the response to biomechanical stimulation

Favero, Giorgia Del; Woelflingseder, Lydia; Janker, Lukas; Neuditschko, Benjamin; Seriani, Stefano; Gallina, Paolo; Sbaizero, Orfeo; Gerner, Christopher; Marko, Doris

doi:10.1038/s41598-018-29728-5

Cited by 16 publications

(25 citation statements)

References 89 publications

(81 reference statements)

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“…To avoid selection bias, image analysis was performed after acquiring all the images form all the experiments and quantification workflow was independently verified with the software Gen5 (BioTek, Winooski, VT). Determination of cell volume and diameter was performed as previously described with the cell counter analyzer CASY-TT (18). Briefly, cells were gently detached with trypsin and after inactivation of the enzyme 100 l cell suspension was diluted in 10 ml CASYton solution.…”

Section: Molecular and Cellular Proteomics 193 479mentioning

confidence: 99%

The Challenge of Classifying Metastatic Cell Properties by Molecular Profiling Exemplified with Cutaneous Melanoma Cells and Their Cerebral Metastasis from Patient Derived Mouse Xenografts

Neuditschko

Janker²,

Niederstaetter³

et al. 2020

Molecular & Cellular Proteomics

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The prediction of metastatic properties from molecular analyses still poses a major challenge. Here we aimed at the classification of metastasis-related cell properties by proteome profiling making use of cutaneous and brain-metastasizing variants from single melanomas sharing the same genetic ancestry. Previous experiments demonstrated that cultured cells derived from these xenografted variants maintain a stable phenotype associated with a differential metastatic behavior: The brain metastasizing variants produce more spontaneous micro-metastases than the corresponding cutaneous variants. Four corresponding pairs of cutaneous and metastatic cells were obtained from four individual patients, resulting in eight cell-lines presently investigated. Label free proteome profiling revealed significant differences between corresponding pairs of cutaneous and cerebellar metastases from the same patient. Indeed, each brain metastasizing variant expressed several apparently metastasis-associated proteomic alterations as compared with the corresponding cutaneous variant. Among the differentially expressed proteins we identified cell adhesion molecules, immune regulators, epithelial to mesenchymal transition markers, stem cell markers, redox regulators and cytokines. Similar results were observed regarding eicosanoids, considered relevant for metastasis, such as PGE2 and 12-HETE. Multiparametric morphological analysis of cells also revealed no characteristic alterations associated with the cutaneous and brain metastasis variants. However, no correct classification regarding metastatic potential was yet possible with the present data. We thus concluded that molecular profiling is able to classify cells according to known functional categories but is not yet able to predict relevant cell properties emerging from networks consisting of many interconnected molecules. The presently observed broad diversity of molecular patterns, irrespective of restricting to one tumor type and two main classes of metastasis, highlights the important need to develop meta-analysis strategies to predict cell properties from molecular profiling data. Such base knowledge will greatly support future individualized precision medicine approaches.

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Section: Molecular and Cellular Proteomics 193 479mentioning

confidence: 99%

The Challenge of Classifying Metastatic Cell Properties by Molecular Profiling Exemplified with Cutaneous Melanoma Cells and Their Cerebral Metastasis from Patient Derived Mouse Xenografts

Neuditschko

Janker²,

Niederstaetter³

et al. 2020

Molecular & Cellular Proteomics

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“…The mechanism of toxic effects of DON is not conclusively explained. As many authors point out, the toxic effects of DON may be the result of dysregulation of immunological and/or neuroendocrine function [14,32]. The cellular mechanism of DON's toxicity is explained by its effect on synthesis of protein and nucleonic acid.…”

Section: Discussionmentioning

confidence: 99%

“…DON enters cell and binds to active ribosomes which transduce a signal to RNA-activated protein kinase (PKR) and hemoitopoeitic cell kinase (Hck). Subsequent phosphorylation of protein kinases drives cells apoptosis and immunotoxic effects [7,14,32].…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Collagen and Elastin Content in Skin of Multiparous Minks Receiving Feed Contaminated with Deoxynivalenol (DON, vomitoxin) with or without Bentonite Supplementation

Taszkun

Tomaszewska

Dobrowolski

et al. 2019

Animals

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Deoxynivalenol (DON, vomitoxin) is considered one of the most dangerous mycotoxins contaminating cereal products for food and feed. One of the protective methods against the adverse effect of DON on mink health is to use a component such as bentonite as a feed supplement to allow toxins absorption. The aim of this study was to determine the effect of DON, administered alone or with bentonite, on the histological structure of the skin and the content of collagen and elastin. A multiparous minks from control group (not exposed to DON) and a study groups receiving fed with DON-containing wheat for seven months: I: at a concentration of 1.1 mg/kg of feed, II: at a concentration of 3.7 mg/kg, III: DON at a concentration of 3.7 mg/kg and bentonite at a concentration of 0.5 kg/1000 kg of feed (0.05%) and IV: DON at a concentration of 3.7 mg/kg and bentonite at a concentration 2 kg/1000 kg (0.2%). After performing euthanasia and before pelting, skin samples of 2 cm in diameter were drawn from the multiparous minks from the lateral surface of the right anterior limb. Our obtained results clearly indicate that DON administered for a period of seven months at a dose of 1.1 mg/kg significantly changes the thickness of skin of a multiparous mink. It causes an increase in the percentage of elastin from 5.9% to 9.4% and a decrease in immature collagen, which results in a change in the collagen/elastin ratio from 10/1 to 5/1. A dose of 3.7 mg/kg DON in feed without or with 0.05% bentonite causes the absence of immature collagen in the dermis, but the addition of 0.2% bentonite in the feed reveals the presence of immature collagen and increase the percentage of the elastin.

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“…modification of membrane curvature/tension [20,21]; ii) re-distribution of transmembrane proteins [22,23]; iii) modulation of ionic fluxes through mechanosensitive ion channels [24][25][26][27]; iv) deformation of cyto-nucleoskeletal elements [28,29]; and v) reorganization of intracellular organelles [30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Integrating Biophysics in Toxicology

Favero

Kraegeloh

2020

Cells

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Integration of biophysical stimulation in test systems is established in diverse branches of biomedical sciences including toxicology. This is largely motivated by the need to create novel experimental setups capable of reproducing more closely in vivo physiological conditions. Indeed, we face the need to increase predictive power and experimental output, albeit reducing the use of animals in toxicity testing. In vivo, mechanical stimulation is essential for cellular homeostasis. In vitro, diverse strategies can be used to model this crucial component. The compliance of the extracellular matrix can be tuned by modifying the stiffness or through the deformation of substrates hosting the cells via static or dynamic strain. Moreover, cells can be cultivated under shear stress deriving from the movement of the extracellular fluids. In turn, introduction of physical cues in the cell culture environment modulates differentiation, functional properties, and metabolic competence, thus influencing cellular capability to cope with toxic insults. This review summarizes the state of the art of integration of biophysical stimuli in model systems for toxicity testing, discusses future challenges, and provides perspectives for the further advancement of in vitro cytotoxicity studies.

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Deoxynivalenol induces structural alterations in epidermoid carcinoma cells A431 and impairs the response to biomechanical stimulation

Cited by 16 publications

References 89 publications

The Challenge of Classifying Metastatic Cell Properties by Molecular Profiling Exemplified with Cutaneous Melanoma Cells and Their Cerebral Metastasis from Patient Derived Mouse Xenografts

The Challenge of Classifying Metastatic Cell Properties by Molecular Profiling Exemplified with Cutaneous Melanoma Cells and Their Cerebral Metastasis from Patient Derived Mouse Xenografts

Evaluation of Collagen and Elastin Content in Skin of Multiparous Minks Receiving Feed Contaminated with Deoxynivalenol (DON, vomitoxin) with or without Bentonite Supplementation

Integrating Biophysics in Toxicology

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