10 research outputs found

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

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    <div><p>Breast cancer is the leading cause of cancer and mortality in women worldwide. Recent studies have argued that there is a close relationship between lipid synthesis and cancer progression because some enzymes related to lipid synthesis are overexpressed in breast cancer tissues. However, lipid distribution in breast cancer tissues has not been investigated. We aimed to visualize phosphatidylcholines (PCs) and lysoPCs (LPCs) in human breast cancer tissues by performing matrix assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), which is a novel technique that enables the visualization of molecules comprehensively. Twenty-nine breast tissue samples were obtained during surgery and subjected to MALDI-IMS analysis. We evaluated the heterogeneity of the distribution of PCs and LPCs on the tissues. Three species [PC(32∶1), PC(34∶1), and PC(36∶1)] of PCs with 1 mono-unsaturated fatty acid chain and 1 saturated fatty acid chain (MUFA-PCs) and one [PC(34∶0)] of PCs with 2 saturated fatty acid chains (SFA-PC) were relatively localized in cancerous areas rather than the rest of the sections (named reference area). In addition, the LPCs did not show any biased distribution. The relative amounts of PC(36∶1) compared to PC(36∶0) and that of PC(36∶1) to LPC(18∶0) were significantly higher in the cancerous areas. The protein expression of stearoyl-CoA desaturase-1 (SCD1), which is a synthetic enzyme of MUFA, showed accumulation in the cancerous areas as observed by the results of immunohistochemical staining. The ratios were further analyzed considering the differences in expressions of the estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki67. The ratios of the signal intensity of PC(36∶1) to that of PC(36∶0) was higher in the lesions with positive ER expression. The contribution of SCD1 and other enzymes to the formation of the observed phospholipid composition is discussed.</p> </div

    The amount of MUFA-PCs relative to SFA-PCs was significantly higher in cancerous areas.

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    <p>(a) The areas that are circled with broken red lines in the hematoxylin and eosin stained image show the cancerous areas. (b) A distribution image of PC(32∶1)+K. (C) A distribution image of PC(32∶0)+K. (d) A distribution image of PC(34∶1)+K. (e) A distribution image of PC(34∶0)+K. (f) A distribution image of PC(36∶1)+K. (g) A distribution image of PC(36∶0)+K. (h) Plot of the intensities of PC(32∶1)+K. (i) Plot of the intensities of PC(32∶0)+K. (j) Plot of the intensities of PC(34∶1)+K. (k) Plot of the intensities of PC(34∶0)+K. (l) Plot of the intensities of PC(36∶1)+K. (m) Plot of the intensities of PC(36∶0)+K. (n) Plot of the ratios of PC(32∶1)+K to PC(32∶0)+K. (o) Plot of the ratios of PC(34∶1)+K to PC(34∶0)+K. (p) Plot of the ratios of PC(36∶1)+K to PC(36∶0)+K.</p

    Pathway for synthesizing MUFA-PCs catalyzed by LPCAT and LPC.

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    <p>Endogenously synthesized mono-unsaturated fatty acids (MUFAs) are converted from saturated fatty acids (SFA) by the catalyzing effect of stearoyl-CoA desaturase-1 (SCD1). A MUFA is added to a lyso-phosphatidylcholine (LPC) through lysophosphatidylcholine acyltransferase (LPCAT) to produce a phosphatidylcholine (PC) that contains MUFA (MUFA-PC). A MUFA-PC is degraded to a LPC and a MUFA by phospholipase A1 (PLA1) and PLA2.</p

    SCD1 expression and the ratios of MUFA-PCs to SFA-PCs and LPCs for differences in ER, HER2, and Ki67 expression.

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    <p>The intensities of SCD staining (a, h, o) and the ratios of MUFA-PC compared to SFA-PC (b–d, i–k, p–r) and LPC (e–g, l–n, s–u) were shown by the differences in ER (a–g), HER2 (h–n), and Ki67 (o–u). All of the cancer lesions were divided into two groups according to the differences in ER, HER2, and Ki67 expression and lesions with less aggressiveness are shown on the left side of each graph.</p

    SCD1 protein was highly expressed in breast cancer tissues.

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    <p>(a) The areas that are circled with broken red lines in the hematoxylin and eosin stained image show cancerous areas. (b) Immunohistochemical staining for stearoyl-CoA desaturase-1 (SCD1) protein. (c) A plot of the intensities of SCD1 between the cancerous areas and the reference areas. (d) Values were plotted as SCD1 intensity on the x-axis and the MUFA-PCs/SFA-PCs ratio on the y-axis. The table shows the frequency of the subjects involved in each quadrant.</p
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