Human Breast Cancer Tissues Contain Abundant Phosphatidylcholine(36∶1) with High Stearoyl-CoA Desaturase-1 Expression

Ide, Yoshimi; Waki, Michihiko; Hayasaka, Takahiro; Nishio, Toshihiro; Morita, Yoshifumi; Tanaka, Hiroki; Sasaki, Takeshi; Koizumi, Kei; Matsunuma, Ryoichi; Hosokawa, Yuko; Ogura, Hironao; Shiiya, Norihiko; Setou, Mitsutoshi

doi:10.1371/journal.pone.0061204

Cited by 113 publications

(101 citation statements)

References 49 publications

(54 reference statements)

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“…All genes had P < 0.05 by ANOVA analysis except LAMB1 , LAMB3 ( P = 0.058), COL4A6 , and COMP . the PC pool, is often associated with paradigms of proliferative cell growth and cell death found in cancer ( 64,65 ), it is interesting to note that changes to both ether-linked PCs and 32:0 PC appear in the transition between steatosis and NASH as highlighted by the LDAbased analysis. The increased levels of 32:0 PC in NASH are likely a result of increased de novo lipid synthesis ( 66 ) and cellular proliferation.…”

Section: Discussionmentioning

confidence: 95%

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic

Gorden

Myers

Ivanova

et al. 2015

Journal of Lipid Research

271

236

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Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common forms of liver disease in Abstract The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for defi nitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profi ling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identifi cation of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of

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Section: Discussionmentioning

confidence: 95%

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic

Gorden

Myers

Ivanova

et al. 2015

Journal of Lipid Research

271

236

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“…Our earlier study showed that breast cancer cells have increased expression of stearoylCoA desaturase 1 (SCD1), the only mammalian fatty acid desaturase. [30] SCD1 is an enzyme that can convert saturated fatty acids to the mono-unsaturated form and preferentially utilizes stearic rather than palmitic acid as a substrate. [31] If fatty acid synthesis were performed when SCD1 is overexpressed, stearic acids would be immediately converted to oleic acids, leaving palmitic acids unchanged.…”

Section: Resultsmentioning

confidence: 99%

Single cell lipidomics of SKBR‐3 breast cancer cells by using time‐of‐flight secondary‐ion mass spectrometry

Ide

Waki

Ishizaki

et al. 2014

Surface & Interface Analysis

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and Mitsutoshi Setou a * Breast cancer is the most common cancer among women worldwide. The molecular characterization of breast tumor cells by using single-cell lipidomics remains relatively unexplored. Here, we introduce a time-of-flight secondary-ion mass spectrometry (TOF-SIMS) approach to visualize the lipids in individual breast cancer cells. The SKBR-3 breast cancer cell line was cultured and dispersed into individual cells. After attachment to a substrate, the cells were rinsed with ammonium acetate and were analyzed using TOF-SIMS. The instrument was operated with Bi 3 2+ as the primary ion. The distributions of ions, including positively charged phosphocholine, and negatively charged phosphates and fatty acids, were simultaneously visualized. These ions were distributed predominantly at the cell attachment sites. The signal intensities of fatty acid ions were determined from the mass spectra at the regions-of-interest. The results of fatty acid analyses on breast cancer cells were consistent with those of our previous study in which prominent expression of stearoyl-CoA desaturase 1 in breast cancer cells was demonstrated. Static TOF-SIMS was shown to be an effective method for determining the lipid molecular signature of the plasma membrane of individual breast cancer cells.

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“…[6,9,10] The increase in the MUFA to SFA ratio is therefore used as an indicator to characterize cancer cells. The ratios of C16 and C18 fatty acids did not show any significant differences (Table 1b).…”

Section: Resultsmentioning

confidence: 99%

“…[5][6][7] In tumor cells, the fatty acid synthesis pathway is activated constitutively to sustain the increasing demand of new membrane phospholipids. [8][9][10] The development of imaging mass spectrometry (IMS) involving matrix-assisted laser desorption/ionization (MALDI)-IMS has contributed to these findings. While MALDI-IMS is effective for directly analyzing biomolecules on the tissue surface at micrometer resolution, [11][12][13] SIMS imaging can be used to analyze a specimen surface at a submicrometer resolution, enabling analyses of the subcellular distribution of molecules in individual cells.…”

Section: Introductionmentioning

confidence: 99%

Glutaraldehyde fixation method for single‐cell lipid analysis by time‐of‐flight secondary ion‐mass spectrometry

Nagata

Ishizaki

Waki

et al. 2014

Surface & Interface Analysis

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Lipid metabolism has attracted much attention in tumor biology studies. Recently, time-of-flight secondary ion-mass spectrometry (TOF-SIMS) imaging has enabled in situ lipid analysis of biological specimens with a submicrometer spatial resolution for analyses of tumor cells. In clinical settings, sample preservation is important, and specimens are often obtained from patients at different times; these samples must be preserved prior to measurement, and preservation techniques commonly involve chemical fixation with aldehydes. However, the influence of sample preservation on TOF-SIMS analysis of fatty acids has not been reported. Thus, we examined the influence of glutaraldehyde fixation on TOF-SIMS analyses by using the multiple myeloma cell line U266. We prepared two indium-tin-oxide-coated glass slides on which cells were attached. One slide was fixed with 0.25% glutaraldehyde and rinsed in ammonium acetate buffer, whereas the other was left untreated. The specimens were subjected to TOF-SIMS analyses in negative-ion mode, and signals in the mass range of m/z 0-1850 were monitored. Both fixed and unfixed cells exhibited intense ion peaks corresponding to phosphoric acids and five types of fatty acids, putatively derived from membrane phospholipids. These ions were localized at the cell attachment site. We statistically compared the mean intensity of fatty acids between fixed and unfixed cells and found that both showed equivalent signals. Glutaraldehyde fixation was thus shown to be an effective method for preparing samples for single-cell lipid analysis by TOF-SIMS.

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Human Breast Cancer Tissues Contain Abundant Phosphatidylcholine(36∶1) with High Stearoyl-CoA Desaturase-1 Expression

Cited by 113 publications

References 49 publications

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic

Single cell lipidomics of SKBR‐3 breast cancer cells by using time‐of‐flight secondary‐ion mass spectrometry

Glutaraldehyde fixation method for single‐cell lipid analysis by time‐of‐flight secondary ion‐mass spectrometry

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