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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)810-819
Number of pages10
JournalProteomics
Volume14
Issue number7-8
DOIs
Publication statusPublished - 2014

Fingerprint

Heterografts
Colonic Neoplasms
Mass spectrometry
Mass Spectrometry
Tissue
Imaging techniques
Amino Acids
Metabolites
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Liver
Ionization
Tumors
Bearings (structural)
Neoplasms
Isoleucine
Hydroxyproline
Glutamine
Phenylalanine
Leucine
Alanine

Keywords

  • Amino acid
  • Cancer metastasis
  • Imaging MS
  • Metabolism
  • On-tissuederivatization
  • Technology

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Medicine(all)

Cite this

Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts. / Toue, Sakino; Sugiura, Yuki; Kubo, Akiko; Ohmura, Mitsuyo; Karakawa, Sachise; Mizukoshi, Toshimi; Yoneda, Junya; Miyano, Hiroshi; Noguchi, Yasushi; Kobayashi, Tsuyoshi; Kabe, Yasuaki; Suematsu, Makoto.

In: Proteomics, Vol. 14, No. 7-8, 2014, p. 810-819.

Research output: Contribution to journalArticle

Toue, Sakino ; Sugiura, Yuki ; Kubo, Akiko ; Ohmura, Mitsuyo ; Karakawa, Sachise ; Mizukoshi, Toshimi ; Yoneda, Junya ; Miyano, Hiroshi ; Noguchi, Yasushi ; Kobayashi, Tsuyoshi ; Kabe, Yasuaki ; Suematsu, Makoto. / Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts. In: Proteomics. 2014 ; Vol. 14, No. 7-8. pp. 810-819.
@article{44bf258c470d4adf8dd50a1213bb5d40,
title = "Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts",
abstract = "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.",
keywords = "Amino acid, Cancer metastasis, Imaging MS, Metabolism, On-tissuederivatization, Technology",
author = "Sakino Toue and Yuki Sugiura and Akiko Kubo and Mitsuyo Ohmura and Sachise Karakawa and Toshimi Mizukoshi and Junya Yoneda and Hiroshi Miyano and Yasushi Noguchi and Tsuyoshi Kobayashi and Yasuaki Kabe and Makoto Suematsu",
year = "2014",
doi = "10.1002/pmic.201300041",
language = "English",
volume = "14",
pages = "810--819",
journal = "Proteomics",
issn = "1615-9853",
publisher = "Wiley-VCH Verlag",
number = "7-8",

}

TY - JOUR

T1 - Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts

AU - Toue, Sakino

AU - Sugiura, Yuki

AU - Kubo, Akiko

AU - Ohmura, Mitsuyo

AU - Karakawa, Sachise

AU - Mizukoshi, Toshimi

AU - Yoneda, Junya

AU - Miyano, Hiroshi

AU - Noguchi, Yasushi

AU - Kobayashi, Tsuyoshi

AU - Kabe, Yasuaki

AU - Suematsu, Makoto

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Amino acid

KW - Cancer metastasis

KW - Imaging MS

KW - Metabolism

KW - On-tissuederivatization

KW - Technology

UR - http://www.scopus.com/inward/record.url?scp=84897423664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897423664&partnerID=8YFLogxK

U2 - 10.1002/pmic.201300041

DO - 10.1002/pmic.201300041

M3 - Article

C2 - 23818158

AN - SCOPUS:84897423664

VL - 14

SP - 810

EP - 819

JO - Proteomics

JF - Proteomics

SN - 1615-9853

IS - 7-8

ER -