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Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

Metabolic signatures differentiate ovarian from colon cancer cell lines

Authors: Anna Halama, Bella S Guerrouahen, Jennifer Pasquier, Ilhem Diboun, Edward D Karoly, Karsten Suhre, Arash Rafii

Published in: Journal of Translational Medicine | Issue 1/2015

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Abstract

Background

In this era of precision medicine, the deep and comprehensive characterization of tumor phenotypes will lead to therapeutic strategies beyond classical factors such as primary sites or anatomical staging. Recently, “-omics” approached have enlightened our knowledge of tumor biology. Such approaches have been extensively implemented in order to provide biomarkers for monitoring of the disease as well as to improve readouts of therapeutic impact. The application of metabolomics to the study of cancer is especially beneficial, since it reflects the biochemical consequences of many cancer type-specific pathophysiological processes. Here, we characterize metabolic profiles of colon and ovarian cancer cell lines to provide broader insight into differentiating metabolic processes for prospective drug development and clinical screening.

Methods

We applied non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography and gas chromatography for the metabolic phenotyping of four cancer cell lines: two from colon cancer (HCT15, HCT116) and two from ovarian cancer (OVCAR3, SKOV3). We used the MetaP server for statistical data analysis.

Results

A total of 225 metabolites were detected in all four cell lines; 67 of these molecules significantly discriminated colon cancer from ovarian cancer cells. Metabolic signatures revealed in our study suggest elevated tricarboxylic acid cycle and lipid metabolism in ovarian cancer cell lines, as well as increased β-oxidation and urea cycle metabolism in colon cancer cell lines.

Conclusions

Our study provides a panel of distinct metabolic fingerprints between colon and ovarian cancer cell lines. These may serve as potential drug targets, and now can be evaluated further in primary cells, biofluids, and tissue samples for biomarker purposes.
Appendix
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Literature
3.
go back to reference Armitage EG, Barbas C (2014) Metabolomics in cancer biomarker discovery: current trends and future perspectives. J Pharm Biomed Anal 87:1–11PubMedCrossRef Armitage EG, Barbas C (2014) Metabolomics in cancer biomarker discovery: current trends and future perspectives. J Pharm Biomed Anal 87:1–11PubMedCrossRef
4.
go back to reference Yada-Hashimoto N, Yamamoto T, Kamiura S, Seino H, Ohira H, Sawai K et al (2003) Metastatic ovarian tumors: a review of 64 cases. Gynecol Oncol 89:314–317PubMedCrossRef Yada-Hashimoto N, Yamamoto T, Kamiura S, Seino H, Ohira H, Sawai K et al (2003) Metastatic ovarian tumors: a review of 64 cases. Gynecol Oncol 89:314–317PubMedCrossRef
5.
go back to reference Nishizuka S, Chen ST, Gwadry FG, Alexander J, Major SM, Scherf U et al (2003) Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling. Cancer Res 63:5243–5250PubMed Nishizuka S, Chen ST, Gwadry FG, Alexander J, Major SM, Scherf U et al (2003) Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling. Cancer Res 63:5243–5250PubMed
6.
go back to reference Fukui Y, Itoh K (2010) A plasma metabolomic investigation of colorectal cancer patients by liquid chromatography-mass spectrometry. Open Anal Chem J 4:1–9CrossRef Fukui Y, Itoh K (2010) A plasma metabolomic investigation of colorectal cancer patients by liquid chromatography-mass spectrometry. Open Anal Chem J 4:1–9CrossRef
7.
go back to reference Odunsi K, Wollman RM, Ambrosone CB, Hutson A, McCann SE, Tammela J et al (2005) Detection of epithelial ovarian cancer using 1H-NMR-based metabonomics. Int J Cancer 113:782–788PubMedCrossRef Odunsi K, Wollman RM, Ambrosone CB, Hutson A, McCann SE, Tammela J et al (2005) Detection of epithelial ovarian cancer using 1H-NMR-based metabonomics. Int J Cancer 113:782–788PubMedCrossRef
8.
go back to reference Ben Sellem D, Elbayed K, Neuville A, Moussallieh F-M, Lang-Averous G, Piotto M et al (2011) Metabolomic characterization of ovarian epithelial carcinomas by HRMAS-NMR spectroscopy. J Oncol 2011:174019PubMedCentralPubMedCrossRef Ben Sellem D, Elbayed K, Neuville A, Moussallieh F-M, Lang-Averous G, Piotto M et al (2011) Metabolomic characterization of ovarian epithelial carcinomas by HRMAS-NMR spectroscopy. J Oncol 2011:174019PubMedCentralPubMedCrossRef
9.
go back to reference Qiu Y, Cai G, Zhou B, Li D, Zhao A, Xie G et al (2014) A distinct metabolic signature of human colorectal cancer with prognostic potential. Clin Cancer Res 20:2136–2146PubMedCrossRef Qiu Y, Cai G, Zhou B, Li D, Zhao A, Xie G et al (2014) A distinct metabolic signature of human colorectal cancer with prognostic potential. Clin Cancer Res 20:2136–2146PubMedCrossRef
10.
go back to reference Cuperlovic-Culf M, Barnett DA, Culf AS, Chute I (2010) Cell culture metabolomics: applications and future directions. Drug Discov Today 15:610–621PubMedCrossRef Cuperlovic-Culf M, Barnett DA, Culf AS, Chute I (2010) Cell culture metabolomics: applications and future directions. Drug Discov Today 15:610–621PubMedCrossRef
11.
go back to reference Böhm A, Halama A, Meile T, Zdichavsky M, Lehmann R, Weigert C et al (2014) Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals. PLoS One 9:e93148PubMedCentralPubMedCrossRef Böhm A, Halama A, Meile T, Zdichavsky M, Lehmann R, Weigert C et al (2014) Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals. PLoS One 9:e93148PubMedCentralPubMedCrossRef
12.
go back to reference Halama A, Moller G, Adamski J (2011) Metabolic signatures in apoptotic human cancer cell lines. OMICS 15:325–335PubMedCrossRef Halama A, Moller G, Adamski J (2011) Metabolic signatures in apoptotic human cancer cell lines. OMICS 15:325–335PubMedCrossRef
13.
go back to reference Halama A, Riesen N, Moller G, Hrabe de Angelis M, Adamski J (2013) Identification of biomarkers for apoptosis in cancer cell lines using metabolomics: tools for individualized medicine. J Intern Med 274:425–439PubMedCrossRef Halama A, Riesen N, Moller G, Hrabe de Angelis M, Adamski J (2013) Identification of biomarkers for apoptosis in cancer cell lines using metabolomics: tools for individualized medicine. J Intern Med 274:425–439PubMedCrossRef
14.
go back to reference Iorio E, Mezzanzanica D, Alberti P, Spadaro F, Ramoni C, D’Ascenzo S et al (2005) Alterations of choline phospholipid metabolism in ovarian tumor progression. Cancer Res 65:9369–9376PubMedCrossRef Iorio E, Mezzanzanica D, Alberti P, Spadaro F, Ramoni C, D’Ascenzo S et al (2005) Alterations of choline phospholipid metabolism in ovarian tumor progression. Cancer Res 65:9369–9376PubMedCrossRef
15.
16.
go back to reference Kastenmuller G, Romisch-Margl W, Wagele B, Altmaier E, Suhre K (2011) MetaP-server: a web-based metabolomics data analysis tool. J Biomed Biotechnol 2011:1-7CrossRef Kastenmuller G, Romisch-Margl W, Wagele B, Altmaier E, Suhre K (2011) MetaP-server: a web-based metabolomics data analysis tool. J Biomed Biotechnol 2011:1-7CrossRef
17.
go back to reference Saeed AI, Sharov V, White J, Li J, Liang W, Bhagabati N et al (2003) TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34:374–378PubMed Saeed AI, Sharov V, White J, Li J, Liang W, Bhagabati N et al (2003) TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34:374–378PubMed
18.
go back to reference Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM et al (2011) Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci USA 108:19611–19616PubMedCentralPubMedCrossRef Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM et al (2011) Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci USA 108:19611–19616PubMedCentralPubMedCrossRef
20.
go back to reference Wagle SR, Morris HP, Weber G (1963) Comparative biochemistry of hepatomas. V. Studies on amino acid incorporation in liver tumors of different growth rates. Cancer Res 23:1003–1007PubMed Wagle SR, Morris HP, Weber G (1963) Comparative biochemistry of hepatomas. V. Studies on amino acid incorporation in liver tumors of different growth rates. Cancer Res 23:1003–1007PubMed
21.
go back to reference Kovacevic Z, Morris HP (1972) The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res 32:326–333PubMed Kovacevic Z, Morris HP (1972) The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res 32:326–333PubMed
22.
go back to reference Hu J, Locasale JW, Bielas JH, O’Sullivan J, Sheahan K, Cantley LC et al (2013) Heterogeneity of tumor-induced gene expression changes in the human metabolic network. Nat Biotechnol 31:522–529PubMedCentralPubMedCrossRef Hu J, Locasale JW, Bielas JH, O’Sullivan J, Sheahan K, Cantley LC et al (2013) Heterogeneity of tumor-induced gene expression changes in the human metabolic network. Nat Biotechnol 31:522–529PubMedCentralPubMedCrossRef
24.
go back to reference Groves AM, Win T, Haim SB, Ell PJ (2007) Non-[18F]FDG PET in clinical oncology. Lancet Oncol 8:822–830PubMedCrossRef Groves AM, Win T, Haim SB, Ell PJ (2007) Non-[18F]FDG PET in clinical oncology. Lancet Oncol 8:822–830PubMedCrossRef
25.
go back to reference DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11–20PubMedCrossRef DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11–20PubMedCrossRef
26.
go back to reference Silva LP, Lorenzi PL, Purwaha P, Yong V, Hawke DH, Weinstein JN et al (2013) Measurement of DNA concentration as a normalization strategy for metabolomic data from adherent cell lines. Anal Chem 85:9536–9542PubMedCrossRef Silva LP, Lorenzi PL, Purwaha P, Yong V, Hawke DH, Weinstein JN et al (2013) Measurement of DNA concentration as a normalization strategy for metabolomic data from adherent cell lines. Anal Chem 85:9536–9542PubMedCrossRef
27.
go back to reference Behrouz Z, JB-M, Wei Hu, Rebecca Stone, Alpa M. Nick, Xinna Zhang et al (2012) Metabolic distinctions in high grade epithelial ovarian cancer. Cancer Res 72(8 Suppl):4802PubMedCrossRef Behrouz Z, JB-M, Wei Hu, Rebecca Stone, Alpa M. Nick, Xinna Zhang et al (2012) Metabolic distinctions in high grade epithelial ovarian cancer. Cancer Res 72(8 Suppl):4802PubMedCrossRef
28.
go back to reference Denkert C, Budczies J, Kind T, Weichert W, Tablack P, Sehouli J et al (2006) Mass spectrometry-based metabolic profiling reveals different metabolite patterns in invasive ovarian carcinomas and ovarian borderline tumors. Cancer Res 66:10795–10804PubMedCrossRef Denkert C, Budczies J, Kind T, Weichert W, Tablack P, Sehouli J et al (2006) Mass spectrometry-based metabolic profiling reveals different metabolite patterns in invasive ovarian carcinomas and ovarian borderline tumors. Cancer Res 66:10795–10804PubMedCrossRef
29.
go back to reference Boss EA, Moolenaar SH, Massuger LF, Boonstra H, Engelke UF, de Jong JG et al (2000) High-resolution proton nuclear magnetic resonance spectroscopy of ovarian cyst fluid. NMR Biomed 13:297–305PubMedCrossRef Boss EA, Moolenaar SH, Massuger LF, Boonstra H, Engelke UF, de Jong JG et al (2000) High-resolution proton nuclear magnetic resonance spectroscopy of ovarian cyst fluid. NMR Biomed 13:297–305PubMedCrossRef
30.
go back to reference Denkert C, Budczies J, Weichert W, Wohlgemuth G, Scholz M, Kind T et al (2008) Metabolite profiling of human colon carcinoma–deregulation of TCA cycle and amino acid turnover. Mol Cancer 7:72PubMedCentralPubMedCrossRef Denkert C, Budczies J, Weichert W, Wohlgemuth G, Scholz M, Kind T et al (2008) Metabolite profiling of human colon carcinoma–deregulation of TCA cycle and amino acid turnover. Mol Cancer 7:72PubMedCentralPubMedCrossRef
31.
go back to reference Loser C, Folsch UR, Paprotny C, Creutzfeldt W (1990) Polyamines in colorectal cancer. Evaluation of polyamine concentrations in the colon tissue, serum, and urine of 50 patients with colorectal cancer. Cancer 65:958–966PubMedCrossRef Loser C, Folsch UR, Paprotny C, Creutzfeldt W (1990) Polyamines in colorectal cancer. Evaluation of polyamine concentrations in the colon tissue, serum, and urine of 50 patients with colorectal cancer. Cancer 65:958–966PubMedCrossRef
32.
go back to reference Gercel-Taylor C, Doering DL, Kraemer FB, Taylor DD (1996) Aberrations in normal systemic lipid metabolism in ovarian cancer patients. Gynecol Oncol 60:35–41PubMedCrossRef Gercel-Taylor C, Doering DL, Kraemer FB, Taylor DD (1996) Aberrations in normal systemic lipid metabolism in ovarian cancer patients. Gynecol Oncol 60:35–41PubMedCrossRef
33.
go back to reference Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033PubMedCentralPubMedCrossRef Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033PubMedCentralPubMedCrossRef
34.
go back to reference Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A et al (2000) Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287:848–851PubMedCrossRef Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A et al (2000) Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287:848–851PubMedCrossRef
35.
go back to reference Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D et al (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30:406–410PubMedCrossRef Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D et al (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30:406–410PubMedCrossRef
36.
37.
go back to reference Gottlieb E, Tomlinson IP (2005) Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer 5:857–866PubMedCrossRef Gottlieb E, Tomlinson IP (2005) Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer 5:857–866PubMedCrossRef
38.
go back to reference Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H et al (1998) Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem 273:23629–23632PubMedCrossRef Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H et al (1998) Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem 273:23629–23632PubMedCrossRef
39.
go back to reference Kaji M, Kabir-Salmani M, Anzai N, Jin CJ, Akimoto Y, Horita A et al (2010) Properties of L-type amino acid transporter 1 in epidermal ovarian cancer. Int J Gynecol Cancer 20:329–336PubMedCrossRef Kaji M, Kabir-Salmani M, Anzai N, Jin CJ, Akimoto Y, Horita A et al (2010) Properties of L-type amino acid transporter 1 in epidermal ovarian cancer. Int J Gynecol Cancer 20:329–336PubMedCrossRef
40.
go back to reference Kennedy EP, Weiss SB (1956) The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem 222:193–214PubMed Kennedy EP, Weiss SB (1956) The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem 222:193–214PubMed
41.
go back to reference Ackerstaff E, Glunde K, Bhujwalla ZM (2003) Choline phospholipid metabolism: a target in cancer cells? J Cell Biochem 90:525–533PubMedCrossRef Ackerstaff E, Glunde K, Bhujwalla ZM (2003) Choline phospholipid metabolism: a target in cancer cells? J Cell Biochem 90:525–533PubMedCrossRef
42.
go back to reference Engelman JA, Luo J, Cantley LC (2006) The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7:606–619PubMedCrossRef Engelman JA, Luo J, Cantley LC (2006) The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7:606–619PubMedCrossRef
44.
go back to reference Giardiello FM, Hamilton SR, Hylind LM, Yang VW, Tamez P, Casero RA Jr et al (1997) Ornithine decarboxylase and polyamines in familial adenomatous polyposis. Cancer Res 57:199–201PubMed Giardiello FM, Hamilton SR, Hylind LM, Yang VW, Tamez P, Casero RA Jr et al (1997) Ornithine decarboxylase and polyamines in familial adenomatous polyposis. Cancer Res 57:199–201PubMed
45.
go back to reference Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H et al (2009) Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res 69:4918–4925PubMedCrossRef Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H et al (2009) Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res 69:4918–4925PubMedCrossRef
46.
go back to reference Roe DS, Roe CR, Brivet M, Sweetman L (2000) Evidence for a short-chain carnitine-acylcarnitine translocase in mitochondria specifically related to the metabolism of branched-chain amino acids. Mol Genet Metab 69:69–75PubMedCrossRef Roe DS, Roe CR, Brivet M, Sweetman L (2000) Evidence for a short-chain carnitine-acylcarnitine translocase in mitochondria specifically related to the metabolism of branched-chain amino acids. Mol Genet Metab 69:69–75PubMedCrossRef
48.
go back to reference Jacob C, Belleville F (1992) l-carnitine: metabolism, functions and value in pathology. Pathol Biol (Paris) 40:910–919 Jacob C, Belleville F (1992) l-carnitine: metabolism, functions and value in pathology. Pathol Biol (Paris) 40:910–919
49.
go back to reference Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O et al (2008) Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 7:45–56PubMedCrossRef Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O et al (2008) Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 7:45–56PubMedCrossRef
Metadata
Title
Metabolic signatures differentiate ovarian from colon cancer cell lines
Authors
Anna Halama
Bella S Guerrouahen
Jennifer Pasquier
Ilhem Diboun
Edward D Karoly
Karsten Suhre
Arash Rafii
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0576-z

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