Palmitic acid, verified by lipid profiling using secondary ion mass spectrometry, demonstrates anti-multiple myeloma activity

Nagata, Yasuyuki; Ishizaki, Itsuko; Waki, Michihiko; Ide, Yoshimi; Hossen, Amir; Ohnishi, Kazunori; Miyayama, Takuya; Setou, Mitsutoshi

doi:10.1016/j.leukres.2015.02.011

Cited by 23 publications

(18 citation statements)

References 55 publications

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“…Recent studies have reported that C 16:0 revealed significant degradation by conversion to a longer-chain fatty acid in breast cancer and hepatocellular carcinoma, and this degradation was caused by the high expression of Elovl6 [36,37]. We have also revealed that C 16:0 and C 16:1 were significantly decreased in MM cells than that in NPCs [29], and this assumption is supported by upregulated Elovl6 mRNA in MM cells found in the cancer microarray database BOncomine^ [38]. Inhibitors of lipid metabolic enzymes are attracting attention as new therapeutic agents [39][40][41].…”

Section: Discussionmentioning

confidence: 52%

“…In our knowledge, no study indicating a direct relationship between this PC (16:0/20:4) and cancer has been reported whereas Guo et al has demonstrated that some polyunsaturated fatty acids (PUFA) and PCs containing PUFA such as C 20:4 and PC(38:4) were significantly decreased in the cancer microenvironment compared with the adjacent normal tissue of six cancer types (breast, lung, colorectal, esophageal, gastric, and thyroid) [32]. We have also reported that C 16:0 was decreased in MM cells than in NPCs by TOF-SIMS analysis [29]. Therefore, the decreased level of PC (16:0/20:4) in MM cells may be due to the decreases of its integrated fatty acid such as C 20:4 and C 16:0 residue of the PC.…”

Section: Discussionmentioning

confidence: 55%

“…Schober et al was the first to develop single-cell MALDI-IMS analysis using the HeLa cell line [27]; however, no report has examined comparative lipid profiling by single-cell MALDI-IMS analysis. Several reports have been published on comparative analysis of single cells using secondary ion mass spectrometry (SIMS), and these reports have demonstrated fatty acid profiles in the single-cell level using clinical samples such as breast cancer stem cell and MM cell [28,29]. Liquid chromatography-MS was also used for analyzing the profile of lipids in a purified cell; however, this method requires extraction and bulk amounts of cells and misses specific information on rare target populations due to the heterogeneity of cells in tissues or groups [28,30].…”

Section: Discussionmentioning

confidence: 99%

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Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells compared to plasma cells: a single-cell MALDI–IMS approach

et al. 2015

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Lipid metabolic changes under diseased conditions, particularly in solid tumors, are attracting increased attention. However, in non-solid tumors, including most hematopoietic tumors, lipid analyses are scarce. Multiple myeloma (MM) is a plasma cell disorder arising from bone marrow, and the lipid status of MM cells has not been reported yet. In this study, we analyzed flow cytometry-sorted single MM cells and normal plasma cells (NPCs) using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), a two-dimensional label-free mass spectrometry technique for biomolecular analysis, to obtain specific lipid information. We isolated 1.31-5.77% of MM cells and 0.03-0.24% of NPCs using fluorescence-activated cell sorting (FACS). Analysis of purified cells using MALDI-IMS at the single-cell level revealed that the peak intensity and ion signals of phosphatidylcholine [PC (16:0/20:4) + H](+) at m/z 782.5 were significantly decreased in MM cells compared to NPCs. By examining particular cell populations rather than cell mixtures, our method can become a suitable tool for the analysis of rare cell populations at the single-cell level and advance the understanding of MM progression.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells compared to plasma cells: a single-cell MALDI–IMS approach

et al. 2015

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“…From both targeted and untargeted lipidomics, we observed significantly lower level of PC in RRMM compared to NDMM, and in high risk compared to low risk patients. Decreased PC was previously observed in MM cells compared to normal plasma cells [8]. Recently, Steiner et al .…”

Section: Discussionmentioning

confidence: 83%

Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome

Mohamed

Collins

Jiang

et al. 2019

Preprint

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17Background: Multiple myeloma (MM) is a hematological malignancy characterized by the 18 clonal expansion of malignant plasma cells. Though durable remissions are possible, MM is 19 considered incurable, with relapse occurring in almost all patients. There has been limited 20 data reported on the lipid metabolism changes in plasma cells during MM progression. Here, 21we evaluated the feasibility of concurrent lipidomics and proteomics analyses from patient 22 plasma cells, and report these data on a limited number of patient samples, demonstrating the 23 feasibility of the method, and establishing hypotheses to be evaluated in the future. 24Methods: Plasma cells were purified from fresh bone marrow aspirates using CD138 25 microbeads. Proteins and lipids were extracted using a bi-phasic solvent system with 26 methanol, methyl tert-butyl ether, and water. Untargeted proteomics, untargeted and targeted 27 lipidomics were performed on 7 patient samples using liquid chromatography-mass 28 spectrometry. Two comparisons were conducted: high versus low risk; relapse versus newly 29 diagnosed. Proteins and pathways enriched in the relapsed group was compared to a public 30 transcriptomic dataset from Multiple Myeloma Research Consortium reference collection 31 (n=222) at gene and pathways level. 32Results: From one million purified plasma cells, we were able to extract material and 33 complete untargeted (~6000 and ~3600 features in positive and negative mode respectively) 34 and targeted lipidomics (313 lipids), as well as untargeted proteomics analysis (~4100 35 reviewed proteins). Comparative analyses revealed limited differences between high and low 36 risk groups (according to the standard clinical criteria), hence we focused on drawing 37 comparisons between the relapsed and newly diagnosed patients. Untargeted and targeted 38 lipidomics indicated significant down-regulation of phosphatidylcholines (PCs) in relapsed 39 MM. Although there was limited overlap of the differential proteins/transcripts, 76 40 Page 3 of 29 significantly enriched pathways in relapsed MM were common between proteomics and 41 transcriptomics data. Further evaluation of transcriptomics data for lipid metabolism network 42 revealed enriched correlation of PC, ceramide, cardiolipin, arachidonic acid and cholesterol 43 metabolism pathways to be exclusively correlated among relapsed but not in newly-44 diagnosed patients. 45 Conclusions:This study establishes the feasibility and workflow to conduct integrated 46 lipidomics and proteomics analyses on patient-derived plasma cells. Potential lipid 47 metabolism changes associated with MM relapse warrant further investigation. 48

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“…In MM, initial lipidomic studies comparing malignant plasma cells to healthy plasma cells have reported decreased levels of phosphatidylcholines [8], and differing fatty acid composition of cellular membranes [8,9]. There are limited studies on the metabolic changes that occur during MM relapse, with most studies focusing at the genomic level [10].…”

Section: Competing Interestsmentioning

confidence: 99%

Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome

et al. 2020

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Background Multiple myeloma (MM) is a hematological malignancy characterized by the clonal expansion of malignant plasma cells. Though durable remissions are possible, MM is considered incurable, with relapse occurring in almost all patients. There has been limited data reported on the lipid metabolism changes in plasma cells during MM progression. Here, we evaluated the feasibility of concurrent lipidomics and proteomics analyses from patient plasma cells, and report these data on a limited number of patient samples, demonstrating the feasibility of the method, and establishing hypotheses to be evaluated in the future. Methods Plasma cells were purified from fresh bone marrow aspirates using CD138 microbeads. Proteins and lipids were extracted using a bi-phasic solvent system with methanol, methyl tertbutyl ether, and water. Untargeted proteomics, untargeted and targeted lipidomics were performed on 7 patient samples using liquid chromatography-mass spectrometry. Two comparisons were conducted: high versus low risk; relapse versus newly diagnosed. Proteins and pathways enriched in the relapsed group was compared to a public transcriptomic dataset from Multiple Myeloma Research Consortium reference collection (n = 222) at gene and pathways level.

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Palmitic acid, verified by lipid profiling using secondary ion mass spectrometry, demonstrates anti-multiple myeloma activity

Cited by 23 publications

References 55 publications

Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells compared to plasma cells: a single-cell MALDI–IMS approach

Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells compared to plasma cells: a single-cell MALDI–IMS approach

Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome

Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome

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