Phospholipids and fatty acids in breast cancer tissue

Punnonen, Kari; Hietanen, Eino; Auvinen, O; Punnonen, R.

doi:10.1007/bf00391361

Cited by 30 publications

(22 citation statements)

References 24 publications

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“…These findings were replicated in our dataset where five of the seven fatty acids found to be increased in tumor tissue can be generated via de novo synthesis. Higher PC and PE levels have been reported previously in breast cancer (31,42,43) and these could be associated with the loss of differentiation and, more specifically, a loss of epithelial polarity. Previous studies have shown that PEs and PCs were upregulated, while p-PEs were downregulated in Madin-Darby canine kidney cells (a cell culture model for epithelial polarization) after the cells underwent epithelial-mesenchymal transition (42).…”

Section: Alterations In Stroma and Glandular Tissue Due To Cancerizatmentioning

confidence: 88%

Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry

et al. 2015

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Breast cancer is a heterogeneous disease characterized by varying responses to therapeutic agents and significant differences in long-term survival. Thus, there remains an unmet need for early diagnostic and prognostic tools and improved histologic characterization for more accurate disease stratification and personalized therapeutic intervention. This study evaluated a comprehensive metabolic phenotyping method in breast cancer tissue that uses desorption electrospray ionization mass spectrometry imaging (DESI MSI), both as a novel diagnostic tool and as a method to further characterize metabolic changes in breast cancer tissue and the tumor microenvironment. In this prospective single-center study, 126 intraoperative tissue biopsies from tumor and tumor bed from 50 patients undergoing surgical resections were subject to DESI MSI. Global DESI MSI models were able to distinguish adipose, stromal, and glandular tissue based on their metabolomic fingerprint. Tumor tissue and tumor-associated stroma showed evident changes in their fatty acid and phospholipid composition compared with normal glandular and stromal tissue. Diagnosis of breast cancer was achieved with an accuracy of 98.2% based on DESI MSI data (PPV 0.96, NVP 1, specificity 0.96, sensitivity 1). In the tumor group, correlation between metabolomic profile and tumor grade/hormone receptor status was found. Overall classification accuracy was 87.7% (PPV 0.92, NPV 0.9, specificity 0.9, sensitivity 0.92). These results demonstrate that DESI MSI may be a valuable tool in the improved diagnosis of breast cancer in the future. The identified tumor-associated metabolic changes support theories of de novo lipogenesis in tumor tissue and the role of stroma tissue in tumor growth and development and overall disease prognosis. Cancer Res; 75(9); 1828-37. Ó2015 AACR.

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Section: Alterations In Stroma and Glandular Tissue Due To Cancerizatmentioning

confidence: 88%

Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry

et al. 2015

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“…41 The concentration of phosphatidylethanolamine (PtdEtn) was described as elevated in tumor tissue. 35,36,42 We have found this increase predominantly in grade 3 mammary carcinoma.…”

Section: Visualization Of Lipid Signalsmentioning

confidence: 92%

“…Others report a decrease of sphingomyelin in tumor tissue (measured as percentage of total phosphorous content) compared with control tissue. 36 Examinations of blood 37 reveal a higher concentration of sphingomyelin in fibroadenoma patients compared to healthy persons.…”

Section: Visualization Of Lipid Signalsmentioning

confidence: 98%

“…Also, increased polyunsaturated fatty acids (PUFA) are reported in tumor tissue. 35,36 The SOM plot shows that the concentration of sphingomyelin-like substances* is elevated predominantly in grade 3 tumors. However, the results concerning sphingomyelin reported in the literature appear rather inconsistent: some authors 35 observe a concentration increase in tumor tissue (measured in mg sphingomyelin/ wet weight).…”

Section: Visualization Of Lipid Signalsmentioning

confidence: 99%

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Visualizing metabolic changes in breast‐cancer tissue using ¹H‐NMR spectroscopy and self‐organizing maps

et al. 2003

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In-vitro NMR spectroscopic examinations of tissue extracts can be combined with appropriate pattern-recognition and visualization techniques in order to monitor characteristic metabolic differences between tissue classes. In the present study, such techniques are applied to a set of 88 breast-tissue samples with the intention of identifying typical differences between various tissue classes. The set contains 49 breast-tumor samples of various tumor grades and 39 samples of healthy tissue. The metabolite compositions of the tissue extracts were investigated using a dual extraction technique and high-resolution (1)H-NMR spectroscopy. The spectra of the hydrophilic and the lipophilic compounds were assigned to three groups according to different malignancy grades of the respective tissue samples. The group characteristics were analyzed using the k-nearest-neighbor method and self-organizing-map visualizations. The results show an increase of UDP-hexose, phosphocholine and phosphoethanolamine concentrations according to the tumor grade. Higher concentrations of taurine were detected in the malignant samples. Myo-inositol and glucose content were elevated in control samples compared with malignant tissue. Both compounds also characterized different subgroups in the pool of unaffected tissue samples depending upon fat content or fibrosis. Several lipid metabolites showed a characteristic elevation with high malignancy.

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“…2) (Punnonen et al 1989;Pizer et al 1998). This explains why in contrast to normal tissues the membrane of tumor cells predominantly contains saturated and monounsaturated fatty acids (Punnonen et al 1989;Lee et al 1995). For de novo synthesis of fatty acids, acetyl CoA and NADPH are necessary.…”

Section: Fatty Acids and Glutamate Two Alternatives For Hydrogen Relmentioning

confidence: 99%

Pyruvate kinase type M2: a crossroad in the tumor metabolome

et al. 2002

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Cell proliferation is a process that consumes large amounts of energy. A reduction in the nutrient supply can lead to cell death by ATP depletion, if cell proliferation is not limited. A key sensor for this regulation is the glycolytic enzyme pyruvate kinase, which determines whether glucose carbons are channelled to synthetic processes or used for glycolytic energy production. In unicellular organisms pyruvate kinase is regulated by ATP, ADP and AMP, by ribose 5-P, the precursor of the nucleic acid synthesis, and by the glycolytic intermediate fructose 1,6-P 2 (FBP), thereby adapting cell proliferation to nutrient supply. The mammalian pyruvate kinase isoenzyme type M2 (M2-PK) displays the same kinetic properties as the pyruvate kinase enzyme from unicellular organisms. The mammalian M2-PK isoenzyme can switch between a less active dimeric form and a highly active tetrameric form which regulates the channeling of glucose carbons either to synthetic processes (dimeric form) or to glycolytic energy production (tetrameric form). Tumor cells are usually characterized by a high amount of the dimeric form leading to a strong accumulation of all glycolytic phosphometabolites above pyruvate kinase. The tetramer-dimer ratio is regulated by ATP, FBP and serine and by direct interactions with different oncoproteins (pp60 v-src , HPV-16 E7). In solid tumors with sufficient oxygen supply pyruvate is supplied by glutaminolysis. Pyruvate produced in glycolysis and glutaminolysis is used for the synthesis of lactate, glutamate and fatty acids thereby releasing the hydrogen produced in the glycolytic glyceraldehyde 3-phosphate dehydrogenase reaction.

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Phospholipids and fatty acids in breast cancer tissue

Cited by 30 publications

References 24 publications

Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry

Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry

Visualizing metabolic changes in breast‐cancer tissue using ¹H‐NMR spectroscopy and self‐organizing maps

Pyruvate kinase type M2: a crossroad in the tumor metabolome

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Phospholipids and fatty acids in breast cancer tissue

Cited by 30 publications

References 24 publications

Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry

Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry

Visualizing metabolic changes in breast‐cancer tissue using 1H‐NMR spectroscopy and self‐organizing maps

Pyruvate kinase type M2: a crossroad in the tumor metabolome

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Visualizing metabolic changes in breast‐cancer tissue using ¹H‐NMR spectroscopy and self‐organizing maps