Abstract 4029: Accumulation of arachidonic acid-containing phosphatidylinositol at the margin of colorectal cancer revealed by imaging mass spectrometry
Authors: Takanori Hiraide, Takanori Sakaguchi, Koji Ikegami, Yoshifumi Morita, Noritaka Masaki, Michihiko Waki, Eiji Sugiyama, Satoru Shinriki, Makoto Takeda, Yasushi Shibasaki, Shinichiro Miyazaki, Atsushi Suzuki, Hirotoshi Kikuchi, Mitsutoshi Setou, Hiroyuki Konno
Journal: Cancer Research (2015)

Abstract [Background] Heterogeneity of neoplastic cells is frequently observed in various neoplastic tumors. Therefore, various cancer cells are supposed to have their cognate functions and show their specific possession of cancer-related proteins. Although some lipids are reported to contribute to tumor progression in several cancers, studies regarding functions and intratumoral distribution of lipids are very limited. [Aim] The aim of this study is to elucidate phospholipids distribution in cancer tissue-originated spheroids (CTOSs) and resected human colorectal cancer (CRC) tissues with imaging mass spectrometer (IMS). [Materials and Methods] We utilized matrix-assisted laser desorption ionization (MALDI)-QIT/TOF-IMS to analyze phospholipids distribution in CTOSs and CRC tissues. Liquid chromatography - tandem mass spectrometer (LC-MS/MS) was used to confirm and quantify the phospholipids. [Results] Among a large number of signals detected in positive and negative ion mode by MALDI-IMS, a molecule with m/z 885.5 in negative ion mode was preferentially observed at surface regions of CTOSs, but not in cell-line-originated spheroids. The molecule was identified as an arachidonic acid (AA)-containing phosophatidylinositol (PI), PI(18:0/20:4), by tandem mass spectrometry analysis. The other AA-containing phospholipids evenly distributed from the surface to the deep inside of CTOS. The amount of this phospholipid, PI(18:0/20:4), was two-fold higher in the surface region of CTOS than in the medial region by LC-MS/MS. Importantly, PI(18:0/20:4) was also strongly detected at the margin (i.e. invasive front) of CRC nest in tumor tissues by MALDI-IMS. [Conclusions] Our study for the first time demonstrates the unique accumulation of AA-containing PI (18:0/20:4) at the margin of CRC nest, which CTOS mimics very well. These data imply the possible importance of this PI for CRC progression including invasion. In addition, further functional analyses of phospholipids would reveal a temporospatial lipid dynamics in heterogeneous tumor tissues and would helpus to seek out novel strategies for personal cancer therapies. Citation Format: Takanori Hiraide, Takanori Sakaguchi, Koji Ikegami, Yoshifumi Morita, Noritaka Masaki, Michihiko Waki, Eiji Sugiyama, Satoru Shinriki, Makoto Takeda, Yasushi Shibasaki, Shinichiro Miyazaki, Atsushi Suzuki, Hirotoshi Kikuchi, Mitsutoshi Setou, Hiroyuki Konno. Accumulation of arachidonic acid-containing phosphatidylinositol at the margin of colorectal cancer revealed by imaging mass spectrometry. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4029. doi:10.1158/1538-7445.AM2015-4029