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Microscopic imaging mass spectrometry assisted by on‐tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts
Author(s) -
Toue Sakino,
Sugiura Yuki,
Kubo Akiko,
Ohmura Mitsuyo,
Karakawa Sachise,
Mizukoshi Toshimi,
Yoneda Junya,
Miyano Hiroshi,
Noguchi Yasushi,
Kobayashi Tsuyoshi,
Kabe Yasuaki,
Suematsu Makoto
Publication year - 2014
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201300041
Subject(s) - derivatization , amino acid , chemistry , alanine , glutamine , biochemistry , leucine , in vivo , mass spectrometry imaging , methionine , glycine , chromatography , mass spectrometry , biology , microbiology and biotechnology
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/γ null 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.