Visualization of the spatial distribution of Pt+ ions in cisplatin-treated glioblastoma cells by time-of-flight secondary ion mass spectrometry

Гулин, А. А.; Pavlyukov, Marat S.; Gularyan, S. K.; Надточенко, В. А.

doi:10.1134/s1990747815020154

Cited by 13 publications

(8 citation statements)

References 23 publications

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“…This result correlates well with previous reports indicating that glutamine accumulation is one of the characteristic features of GBM (36). In addition, we have also observed a reduced amount of monoacylglyceride C18:1 (m/z = 339,29 (28,37)) in tumor tissue, which also made it possible to clearly distinguish GBM from the normal brain (Fig. 1C).…”

Section: Downloaded Fromsupporting

confidence: 92%

Investigation of Inter- and Intratumoral Heterogeneity of Glioblastoma Using TOF-SIMS

Gularyan

Гулин

Anufrieva

et al. 2020

Molecular & Cellular Proteomics

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Glioblastoma (GBM) is one of the most aggressive human cancers with a median survival of less than two years. A distinguishing pathological feature of GBM is a high degree of inter- and intratumoral heterogeneity. Intertumoral heterogeneity of GBM has been extensively investigated on genomic, methylomic, transcriptomic, proteomic and metabolomics levels, however only a few studies describe intratumoral heterogeneity because of the lack of methods allowing to analyze GBM samples with high spatial resolution. Here, we applied TOF-SIMS (Time-of-flight secondary ion mass spectrometry) for the analysis of single cells and clinical samples such as paraffin and frozen tumor sections obtained from 57 patients. We developed a technique that allows us to simultaneously detect the distribution of proteins and metabolites in glioma tissue with 800 nm spatial resolution. Our results demonstrate that according to TOF-SIMS data glioma samples can be subdivided into clinically relevant groups and distinguished from the normal brain tissue. In addition, TOF-SIMS was able to elucidate differences between morphologically distinct regions of GBM within the same tumor. By staining GBM sections with gold-conjugated antibodies against Caveolin-1 we could visualize border between zones of necrotic and cellular tumor and subdivide glioma samples into groups characterized by different survival of the patients. Finally, we demonstrated that GBM contains cells that are characterized by high levels of Caveolin-1 protein and cholesterol. This population may partly represent a glioma stem cells. Collectively, our results show that the technique described here allows to analyze glioma tissues with a spatial resolution beyond reach of most of other omics approaches and the obtained data may be used to predict clinical behavior of the tumor.

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Section: Downloaded Fromsupporting

confidence: 92%

Investigation of Inter- and Intratumoral Heterogeneity of Glioblastoma Using TOF-SIMS

Gularyan

Гулин

Anufrieva

et al. 2020

Molecular & Cellular Proteomics

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“…Therefore, in addition to the FLIM study described above we also performed a detailed analysis of lipid composition from our cell samples by ToF-SIMS. www.nature.com/scientificreports/ In order to test possible correlations of the lipid composition with changes in membrane viscosity, lipid analysis on the 21st day of differentiation was performed by ToF-SIMS, based on comparison of signal intensity of known lipid species [25][26][27] (Fig. 5).…”

Section: Lipid Analysis Of Mscs Membrane During Differentiation By Tomentioning

confidence: 99%

“…A low-energy electron flood gun was activated to avoid charging effects. Ion yields were calculated as an intensity of the corresponding peak of interest normalized to the total ion count amount 26 .…”

Section: Tof-sims Analysismentioning

confidence: 99%

Monitoring membrane viscosity in differentiating stem cells using BODIPY-based molecular rotors and FLIM

Kashirina

López‐Duarte

Kubánková

et al. 2020

Sci Rep

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Membrane fluidity plays an important role in many cell functions such as cell adhesion, and migration. In stem cell lines membrane fluidity may play a role in differentiation. Here we report the use of viscosity-sensitive fluorophores based on a BODIPY core, termed "molecular rotors", in combination with Fluorescence Lifetime Imaging Microscopy, for monitoring of plasma membrane viscosity changes in mesenchymal stem cells (MSCs) during osteogenic and chondrogenic differentiation. In order to correlate the viscosity values with membrane lipid composition, the detailed analysis of the corresponding membrane lipid composition of differentiated cells was performed by timeof-flight secondary ion mass spectrometry. Our results directly demonstrate for the first time that differentiation of MSCs results in distinct membrane viscosities, that reflect the change in lipidome of the cells following differentiation. Membrane fluidity is considered a key parameter influencing biological function of cells, such as cell adhesion, migration and differentiation 1. These properties are of particular importance in stem cell lines, where small modifications in membrane parameters have the potential to either promote a lineage commitment or a selfrenewal 2. The plasma membrane is the interface between a cell and its environment, it directly interacts with the matrix outside the cell and is responsible for many important tasks such as signaling and mass transfer. In stem cells, its composition and properties are likely to reflect their differentiation status. However, little is known on how the viscosity parameters of different stem cell lineages can change depending on the direction of differentiation. There is evidence that the membrane fluidity substantially changes during induced pluripotent stem cells (iPS) differentiation. Generalized polarization monitoring was previously used to detect the rise of membrane rigidity during iPSC differentiation 1. Furthermore, the results in 1 potentially suggested that membrane rigidification could be transmitted to neighboring cells, resulting in the acceleration of a cells differentiation, in a wave-line fashion. It was also reported that the viscoelastic properties can predict which subpopulations of undifferentiated mesenchymal stem cells (MSCs) differentiate into osteocytes, and which would turn into adipocytes or chondroblasts. The stiffest cell populations produced more bone cells; the softest cells predominantly produced fat cells; the cells with the highest viscosity became cartilage cells 3. While cell stiffness measured in 3 is a distinctly different property to the cell membrane viscosity, both depend on membrane lipid compositions. There is evidence that differentiation of human mesenchymal stem cells (MSCs) into osteoblasts, chondrocytes or adipocytes produces specific membrane compositions and biophysical properties,

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“…TOF‐SIMS was one of the first mass spectrometry techniques applied to IMS. To date, TOF‐SIMS has been used to study biomolecular distribution of surfaces or subsurfaces such as human tissues (breast tumor, glioblastoma cells, and neuronal cells), microbes, and nematodes . Because of the high spatial resolution (~nm) in TOF‐SIMS‐IMS, it is capable of analyzing molecular distribution at the single‐cell level .…”

Section: Vacuum Ionization Imaging Mass Spectrometry Systemsmentioning

confidence: 99%

Imaging mass spectrometry for metabolites: technical progress, multimodal imaging, and biological interactions

Shu

Yang

2017

WIREs Mechanisms of Disease

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Imaging mass spectrometry (IMS) allows the study of the spatial distribution of small molecules in biological samples. IMS is able to identify and quantify chemicals in situ from whole tissue sections to single cells. Both vacuum mass spectrometry (MS) and ambient MS systems have advanced considerably over the last decade; however, some limitations are still hard to surmount. Sample pretreatment, matrix or solvent choices, and instrument improvement are the key factors that determine the successful application of IMS to different samples and analytes. IMS with innovative MS analyzers, powerful MS spectrum databases, and analysis tools can efficiently dereplicate, identify, and quantify natural products. Moreover, multimodal imaging systems and multiple MS-based systems provide additional structural, chemical, and morphological information and are applied as complementary tools to explore new fields. IMS has been applied to reveal interactions between living organisms at molecular level. Recently, IMS has helped solve many previously unidentifiable relations between bacteria, fungi, plants, animals, and insects. Other significant interactions on the chemical level can also be resolved using expanding IMS techniques. WIREs Syst Biol Med 2017, 9:e1387. doi: 10.1002/wsbm.1387 For further resources related to this article, please visit the WIREs website.

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Visualization of the spatial distribution of Pt+ ions in cisplatin-treated glioblastoma cells by time-of-flight secondary ion mass spectrometry

Cited by 13 publications

References 23 publications

Investigation of Inter- and Intratumoral Heterogeneity of Glioblastoma Using TOF-SIMS

Investigation of Inter- and Intratumoral Heterogeneity of Glioblastoma Using TOF-SIMS

Monitoring membrane viscosity in differentiating stem cells using BODIPY-based molecular rotors and FLIM

Imaging mass spectrometry for metabolites: technical progress, multimodal imaging, and biological interactions

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