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人乳腺癌组织中含有丰富的具有高硬脂酰辅酶 A 去饱和酶-1 表达的磷脂酰胆碱(36∶1)。

Human breast cancer tissues contain abundant phosphatidylcholine(36∶1) with high stearoyl-CoA desaturase-1 expression.

机构信息

Department of Surgery I, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

PLoS One. 2013 Apr 16;8(4):e61204. doi: 10.1371/journal.pone.0061204. Print 2013.

Abstract

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(34:1) to that of PC(34:0) was higher in the lesions with positive ER expression [corrected]. The contribution of SCD1 and other enzymes to the formation of the observed phospholipid composition is discussed.

摘要

乳腺癌是全球女性癌症和死亡的主要原因。最近的研究表明,脂质合成与癌症进展之间存在密切关系,因为一些与脂质合成相关的酶在乳腺癌组织中过度表达。然而,乳腺癌组织中的脂质分布尚未得到研究。我们旨在通过基质辅助激光解吸/电离-成像质谱(MALDI-IMS)来可视化人乳腺癌组织中的磷脂酰胆碱(PCs)和溶血磷脂酰胆碱(LPCs),MALDI-IMS 是一种能够全面可视化分子的新技术。在手术过程中获得了 29 个乳腺组织样本,并进行了 MALDI-IMS 分析。我们评估了 PCs 和 LPCs 在组织上分布的异质性。三种具有 1 个单不饱和脂肪酸链和 1 个饱和脂肪酸链的 PC(PC(32∶1)、PC(34∶1)和 PC(36∶1))和两种具有 2 个饱和脂肪酸链的 PC(PC(34∶0))相对定位于癌区而不是其余部分(称为参考区)。此外,LPC 没有显示任何偏向性分布。与 PC(36∶0)相比,PC(36∶1)的相对量和 PC(36∶1)与 LPC(18∶0)的相对量在癌区显著更高。免疫组织化学染色结果显示,作为 MUFA 合成酶的硬脂酰辅酶 A 去饱和酶-1(SCD1)的蛋白表达在癌区积聚。进一步分析了考虑到雌激素受体(ER)、人表皮生长因子受体 2(HER2)和 Ki67 的表达差异的比值。在 ER 表达阳性的病变中,PC(34:1)与 PC(34:0)的信号强度比值更高[校正]。讨论了 SCD1 和其他酶对观察到的磷脂组成形成的贡献。

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