Accumulation of arachidonic acid-containing phosphatidylinositol at the outer edge of colorectal cancer.

Takanori Hiraide,Shinichiro Miyazaki,Satoru Shinriki,Masahiro Inoue,Hiroyuki Konno,Eiji Sugiyama,Michihiko Waki,Hiroaki Okuyama,Yasushi Shibasaki,Takahiro Hayasaka,Hirotoshi Kikuchi,Koji Ikegami,Mitsutoshi Setou,Makoto Takeda,Yoshifumi Morita,Takanori Sakaguchi,Noritaka Masaki

doi:10.1038/srep29935

Abstract

Accumulating evidence indicates that cancer cells show specific alterations in phospholipid metabolism that contribute to tumour progression in several types of cancer, including colorectal cancer. Questions still remain as to what lipids characterize the outer edge of cancer tissues and whether those cancer outer edge-specific lipid compositions emerge autonomously in cancer cells. Cancer tissue-originated spheroids (CTOSs) that are composed of pure primary cancer cells have been developed. In this study, we aimed to seek out the cancer cell-autonomous acquisition of cancer outer edge-characterizing lipids in colorectal cancer by analysing phospholipids in CTOSs derived from colorectal cancer patients with matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS). A signal at m/z 885.5 in negative ion mode was detected specifically at the surface regions. The signal was identified as an arachidonic acid (AA)-containing phosphatidylinositol (PI), PI(18:0/20:4), by tandem mass spectrometry analysis. Quantitative analysis revealed that the amount of PI(18:0/20:4) in the surface region of CTOSs was two-fold higher than that in the medial region. Finally, PI(18:0/20:4) was enriched at the cancer cells/stromal interface in colorectal cancer patients. These data imply a possible importance of AA-containing PI for colorectal cancer progression, and suggest cells expressing AA-containing PI as potential targets for anti-cancer therapy.

Highlights

The outer edge of cancer tissue is thought to have unique characteristics, which underlie the property of cancer progression and invasion[19,20,21]
We attempted to reveal phospholipids that characterized the outer edge of colorectal cancer cells, and found an AA-containing PI, PI(18:0/20:4) as a cancer outer edge-characterizing phospholipid in colorectal tumours
We first noticed a unique distribution of an AA-containing PI, PI(18:0/20:4), in cancer tissue-originated spheroids (CTOSs) originating from colorectal cancer patients, but not in multicellular tumour spheroids (MCTSs) derived from homogeneous cell lines

Summary

Introduction

The outer edge of cancer tissue is thought to have unique characteristics, which underlie the property of cancer progression and invasion[19,20,21]. Epithelial-mesenchymal transition (EMT), an important process for tumour invasion, is induced by the interaction between tumour cells at the invasive front and cells in the invaded regions[22] Despite these findings, it still remains unclear whether the acquisition of characteristics/properties of cancer outer edge occurs in cancer cells autonomously. CTOSs retain characteristics of the original tumours, such as KRAS and BRAF mutations, and have potential to be used in evaluating chemosensitivity of cancer cells derived from individual patients. Despite these advances, spheroids including CTOSs have not been examined in detail. We provided evidence for an accumulation of an arachidonic acid-containing phosphatidylinositol in the surface of CTOSs and at the outer edge of colorectal cancer cells

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