Abstract 2511: Comprehensive metabolic profiling of hepatocellular carcinoma and pancreatic tumors by capillary electrophoresis-mass spectrometry.

Abstract

Abstract (Background) Most cancer types have been widely known to generate energy primarily by glycolysis rather than oxidative phosphorylation even under normoxia (Warburg effect). However, inadequate blood supply resulting from defective angiogenesis is often observed in different kinds of cancer tissues, and their microenvironment is considered nutritionally unfavorable. How these cancer cells generate ATP is therefore still unclear. We previously reported enhanced glycolysis and significant accumulation of all amino acids except glutamine in both colon and stomach cancer tissues (Hirayama A, et al Cancer Res 2009). (Methods) Here, we investigated the metabolic microenvironment of hepatocelluar carcinoma (HCC)(n=28, HBV-positive (B) 7, HCV-positive (C) 6, NonBnonC (NBNC) 15), and pancreatic tumors (n=40, Invasive ductal adenocarcinoma (PDAC) 21, Intraductal papillary mucinous adenoma (IPMA) 5, Intraductal papillary mucinous carcinoma (IPMC) 14), using capillary electrophoresis-mass spectrometry (CE-MS). (Results) The amount of glucose were more than ten times higher in liver tissues, which indicates that liver tissue exist in nutritionally favorable microenvironment even in tumor tissue compared with pancreas tissue. Significant lactate accumulation was found in all cancer tissues (HCC, IPMC, and PDAC), which imply enhanced glycolysis. However, significant organ-specific differences were found in the levels of amino acids. Organ and etiology-specific difference were found in intermediates of TCA cycle. For example, citrate was increased in B-HCC, malate was decreased in NBNC-HCC, fumarate was decreased in B-HCC, NBNC-HCC, and PDAC, citrate was decreased in IPMC, iso-citrate was decreased in PDAC, compared to normal tissue, significantly. The concentration of most amino acids were not changed between normal and tumor tissues in HCC and pancreatic tumors, which suggests that these type of cancers do not depend on autophagy for their amino acid source. (Conclusions)Overall, these results provide metabolic phenotypes of different cancer tissues that reflect the tumor microenvironment. Citation Format: Motohisa Tada, Akiyoshi Hirayama, Fumihiko Kanai, Hideyuki Yoshitomi, Masayuki Ohtsuka, Masaru Miyazaki, Tomoyoshi Soga, Osamu Yokosuka. Comprehensive metabolic profiling of hepatocellular carcinoma and pancreatic tumors by capillary electrophoresis-mass spectrometry. [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 2511. doi:10.1158/1538-7445.AM2013-2511