Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts

Sakino Toue, Yuki Sugiura, Akiko Kubo, Mitsuyo Ohmura, Sachise Karakawa, Toshimi Mizukoshi, Junya Yoneda, Hiroshi Miyano, Yasushi Noguchi, Tsuyoshi Kobayashi, Yasuaki Kabe, Makoto Suematsu

研究成果: Article査読

49 被引用数 (Scopus)

抄録

Imaging MS combined with CE/MS serves as a method to provide semi-quantitative and spatial information of small molecular metabolites in tissue slices. However, not all metabolites including amino acids have fully been visualized, because of low-ionization efficiency in MALDI MS. This study aimed to acquire semi-quantitative spatial information for multiple amino acids in frozen tissue slices. As a derivatization reagent, p-N,N,N-trimethylammonioanilyl N'-hydroxysuccinimidyl carbamate iodide (TAHS) was applied to increase their ionization efficiency and detection sensitivity. Semi-quantitative MALDI-imaging MS allowed us to visualize and quantify free amino acid pools in human colon cancer xenografts using a model of liver metastases in super-immunodeficient NOD/scid/γnull mice (NOG mice). Because the m/z values of several TAHS-derivatized amino acids overlap with those of the 2,5-dihydroxybenzoic acid background and other endogenous compounds, we imaged them with tandem MS. The results indicated that regional contents of glutamate, glutamine, glycine, leucine/isoleucine/hydroxyproline, phenylalanine, and alanine were significantly elevated in metastatic tumors versus parenchyma of tumor-bearing livers. On-tissue TAHS derivatization thus serves as a useful method to detect alterations in many amino acid levels in vivo, thereby enabling understanding of the spatial alterations of these metabolites under varied disease conditions including cancer.

本文言語English
ページ(範囲)810-819
ページ数10
ジャーナルProteomics
14
7-8
DOI
出版ステータスPublished - 2014 4月

ASJC Scopus subject areas

  • 生化学
  • 分子生物学

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