Single cell mass spectrometry analysis of drug-resistant cancer cells: Metabolomics studies of synergetic effect of combinational treatment

Chen, Xingxiu; Sun, Mei; Yang, Zhibo

doi:10.1016/j.aca.2022.339621

Cited by 21 publications

(21 citation statements)

References 63 publications

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“…A wide multitude of research activities have been focused on immune evasion and drug resistance to overcome therapeutic resistance. Chen et al utilized the single-probe mass spectrometry technique to analyze live irinotecan-resistant (IRI) cells under different treatment conditions, demonstrating a metformin-IRI synergistic effect overcoming drug resistance (117). Inhibition of fatty acid synthase (FASN) is a potential mechanism related to metformin treatment of drug-resistant cancer cells, which results in the downregulation of lipids and fatty acids.…”

Section: Therapeutic Resistancementioning

confidence: 99%

Single-Cell Metabolomics in Hematopoiesis and Hematological Malignancies

Zuo

2022

Front. Oncol.

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Aberrant metabolism contributes to tumor initiation, progression, metastasis, and drug resistance. Metabolic dysregulation has emerged as a hallmark of several hematologic malignancies. Decoding the molecular mechanism underlying metabolic rewiring in hematological malignancies would provide promising avenues for novel therapeutic interventions. Single-cell metabolic analysis can directly offer a meaningful readout of the cellular phenotype, allowing us to comprehensively dissect cellular states and access biological information unobtainable from bulk analysis. In this review, we first highlight the unique metabolic properties of hematologic malignancies and underscore potential metabolic vulnerabilities. We then emphasize the emerging single-cell metabolomics techniques, aiming to provide a guide to interrogating metabolism at single-cell resolution. Furthermore, we summarize recent studies demonstrating the power of single-cell metabolomics to uncover the roles of metabolic rewiring in tumor biology, cellular heterogeneity, immunometabolism, and therapeutic resistance. Meanwhile, we describe a practical view of the potential applications of single-cell metabolomics in hematopoiesis and hematological malignancies. Finally, we present the challenges and perspectives of single-cell metabolomics development.

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Section: Therapeutic Resistancementioning

confidence: 99%

Single-Cell Metabolomics in Hematopoiesis and Hematological Malignancies

Zuo

2022

Front. Oncol.

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“…MS is also emerging as a key technology in the detection of lipids from single cells; however, there are some limitations in the sensitivity and/or specificity of currently available technologies. Commonly used ionization techniques for lipid single cell analysis include matrix-assisted laser desorption ionization (1-10), secondary ion mass spectrometry (11)(12)(13), laser ablation electrospray ionization (14,15), nanospray desorption electrospray ionization (16) and nanoelectrospray ionization (NanoESI) (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). NanoESI capillaries are an ideal size for directly sampling and infusing the contents of a single cell into the mass spectrometer, but this process is quite laborious and requires the use of micromanipulators for handling and sampling from single cells which limits its throughput.…”

Section: Introductionmentioning

confidence: 99%

“…NanoESI capillaries are an ideal size for directly sampling and infusing the contents of a single cell into the mass spectrometer, but this process is quite laborious and requires the use of micromanipulators for handling and sampling from single cells which limits its throughput. Some improvements to the throughput of the technique have been made through the use of a continuous sampling arm that uses dual-bore quartz needles to sample from cells located on a movable stage (i.e., single probe MS) (21)(22)(23)(26)(27)(28). However, the spray 4 duration per cell is limited (~3 min) which precludes the acquisition of tandem mass spectrometry data from all but the most abundant metabolites (26).…”

Section: Introductionmentioning

confidence: 99%

FACS-assisted single-cell lipidome analysis of phosphatidylcholines and sphingomyelins

Hancock

Ding

Beves

et al. 2022

Preprint

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Recent advances in single-cell genomics and transcriptomics technologies have transformed our understanding of cellular heterogeneity in growth, development, ageing and disease. Despite these advances, however, single-cell metabolite profiling (i.e., metabolomics) methods have comparatively lagged behind due to limitations in technology. We have developed a high-throughput method for the detection and quantification of a wide range of phosphatidylcholine (PC) and sphingomyelin (SM) species from single cells that combines fluorescence-assisted cell sorting (FACS) with automated chip-based nanoelectrospray ionisation (nanoESI) and shotgun lipidomics. We show herein that our method is capable of quantifying more than 50 different PC and SM species from single cells and can easily distinguish between cells of different lineages or cells treated with exogenous fatty acids. Moreover, our method can detect more subtle differences in the lipidome between cell lines of the same cancer type. Our approach has the capacity to be run in parallel with other single-cell technologies to deliver near-complete multi-omics data on cells with a similar phenotype and has the capacity to significantly advance our current knowledge on cellular heterogeneity.

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“…In addition, intracellular metabolites are rapidly altered by variations in the surrounding environment . Methods based on HPLC-MS also require complex sample preparation processes (e.g., cell lysis and metabolite extraction), which inevitably change the metabolic process and molecular composition in cells . These processes can also result in the loss of metabolites with rapid turnover, making it difficult to accurately reflect the metabolic profiles in living cells.…”

mentioning

confidence: 99%

“…14 Methods based on HPLC-MS also require complex sample preparation processes (e.g., cell lysis and metabolite extraction), which inevitably change the metabolic process and molecular composition in cells. 15 These processes can also result in the loss of metabolites with rapid turnover, making it difficult to accurately reflect the metabolic profiles in living cells. Moreover, separating samples with HPLC is timeconsuming, which is not conducive to rapid and direct detection and analysis of metabolites.…”

mentioning

confidence: 99%

Single-Cell Metabolomics-Based Strategy for Studying the Mechanisms of Drug Action

et al. 2023

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Studying the mechanisms of drug antitumor activity at the single-cell level can provide information about the responses of cell subpopulations to drug therapy, which is essential for the accurate treatment of cancer. Due to the small size of single cells and the low contents of metabolites, metabolomics-based approaches to studying the mechanisms of drug action at the single-cell level are lacking. Herein, we develop a label-free platform for studying the mechanisms of drug action based on single-cell metabolomics (sMDA-scM) by integrating intact living-cell electro-launching ionization mass spectrometry (ILCEI-MS) with metabolomics analysis. Using this platform, we reveal that non-small-cell lung cancer (NSCLC) cells treated by gefitinib can be clustered into two cell subpopulations with different metabolic responses. The glutathione metabolic pathway of the subpopulation

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Single cell mass spectrometry analysis of drug-resistant cancer cells: Metabolomics studies of synergetic effect of combinational treatment

Cited by 21 publications

References 63 publications

Single-Cell Metabolomics in Hematopoiesis and Hematological Malignancies

Single-Cell Metabolomics in Hematopoiesis and Hematological Malignancies

FACS-assisted single-cell lipidome analysis of phosphatidylcholines and sphingomyelins

Single-Cell Metabolomics-Based Strategy for Studying the Mechanisms of Drug Action

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