Abstract 719: Accumulation of amino acids in metastatic foci of human colon cancer xenografts revealed by newly developed method for imaging mass spectrometry of amino acids.

Abstract

Abstract MALDI imaging mass spectrometry (IMS) provides information about the spatial distribution of metabolites within thin slices of tissue, and has been used to elucidate complex phenotypes under various physiological conditions. Previously, our group reported distinct spatial distribution of a variety of metabolites in experimental model of hepatic micrometastasis of the solid tumor. However the metabolic properties in tumor and host tissues are not fully characterized, because of difficulty in visualizing most amino acids, due to their lower ionization efficiency. Here, by using of p-N,N,N-trimethylammonioanily N’-hydroxysuccinimidyl carbamate iodide (TAHS) as a derivatizing reagent, we have successfully developed the method for the detection of various amino acids simultaneously by MALDI-MS on tissue section. We prepared liver section from hepatic metastasis model of human colon cancer, and then performed MALDI-IMS. To compare the signal intensities of amino acids among the different sections, we normalized the MALDI-IMS data with the quantified value of each amino acid obtained from capillary electrophoresis-mass spectrometry. The result indicated the amount of glycine, phenylalanine, leucine, glutamate, and glutamine were significantly elevated in metastatic foci compared to liver parenchyma. Other metabolites such as ATP and glutathione also accumulated in metastatic foci, and these results suggested that increased amino acid pool were required to maintain ATP and GSH levels in tumor. In conclusion, we have demonstrated that novel imaging technique by using of IMS combined with on-tissue TAHS derivatization enables the visualization of amino acid distribution in tissue. The current method could be powerful tool to elucidate the mechanism for metabolic changes of cancer disease in vivo. Citation Format: Sakino Toue, Yuki Sugiura, Akiko Kubo, Mitsuyo Ohmura, Sachise Karakawa, Toshimi Mizukoshi, Junya Yoneda, Hiroshi Miyano, Yasushi Noguchi, Tsuyoshi Kobayashi, Yasuaki Kabe, Makoto Suematsu. Accumulation of amino acids in metastatic foci of human colon cancer xenografts revealed by newly developed method for imaging mass spectrometry of amino acids. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 719. doi:10.1158/1538-7445.AM2013-719