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

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

doi:10.1371/journal.pone.0061204

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(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.

Highlights

Breast cancer is the leading cause of cancer and cancer related mortality in women worldwide [1]
Since the samples that were used for imaging mass spectrometry (IMS) analysis were severely destroyed by laser irradiation, hematoxylin and eosin (HE)-stained images of adjacent sections were used for the identification of cancerous areas and are presented in the figures
The cancerous areas are indicated by broken red lines, and the stromal tissues that were around the ducts are circled with broken yellow lines in the HEstained image (Figure 2a)

Summary

Introduction

Breast cancer is the leading cause of cancer and cancer related mortality in women worldwide [1]. The activation of lipid metabolism in breast cancer cells has been increasingly recognized as a hallmark of carcinogenesis [2,3]. Phosphatidylcholines (PCs) are generally the most abundant phospholipid species in mammalian cells, and PC synthesis and metabolism in cancer progression have been investigated [4]. Aberrancy in PC metabolism, which is mainly through the increased degradation of PCs, was indicated in a study using nuclear magnetic resonance for the analysis of breast cancer cell lines; they did not distinguish the acyl chain structures of the PCs [5,6,7]. The characterization of breast cancer tissues from patients by differentiating among molecular species of PCs has been reported by using gas chromatography [8] and liquid chromatography/mass spectrometry [9]. Biomarker investigation by lipidomic analysis including several PC species has been proposed for several PC species as putative diagnostic markers and therapeutic targets [9]

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