title: Changes in glucose metabolism and gene expression after transfer of anti-angiogenic genes in rat hepatoma.
abstract: OBJECTIVE
  Human troponin I (TROP), the soluble receptor for vascular endothelial growth factor (sFLT) and angiostatin (ASTAT) are potent inhibitors of endothelial cell proliferation, angiogenesis and tumour growth in vivo. Transfer of these genes into tumours may induce changes not only in perfusion, but also more general ones such as changes in metabolism. The aim of this study was to assess these reactions using FDG-PET and high-throughput methods such as gene profiling.
  
  
  METHODS
  We established Morris hepatoma (MH3924A) cell lines expressing TROP, sFLT or ASTAT and quantified (18)F-fluorodeoxyglucose ((18)FDG) uptake by dynamic positron emission tomography (PET) after tumour inoculation in ACI rats. Furthermore, expression of glucose transporter-1 and -3 (GLUT-1 and GLUT-3) as well as hexokinase-1 and -2 were investigated by RT-PCR and immunohistomorphometry. In addition, gene array analyses were performed.
  
  
  RESULTS
  (18)FDG uptake, vascular fraction and distribution volume were significantly higher in all genetically modified tumours. Immunohistomorphometry showed an increased percentage of hexokinase-1 and -2 as well as GLUT-1 and -3 immunoreactive (ir) cells. Using gene arrays and comparing all three groups of genetically modified tumours, we found upregulated expression of 36 genes related to apoptosis, signal transduction, stress or metabolism.
  
  
  CONCLUSIONS
  TROP-, sFLT- or ASTAT-expressing MH3924A tumours show enhanced influx of (18)FDG, which seems to be caused by several factors: enhanced exchange of nutrients between blood and tumour, increased amounts of glucose transporters and hexokinases, and increased expression of genes related to apoptosis, matrix and stress, which induce an increased demand for glucose.
authors: Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany. Uwe_Haberkorn@med.uni-heidelberg.de
authors: Uwe
authors: U
authors: Haberkorn
authors: Johannes
authors: J
authors: Hoffend
authors: Kerstin
authors: K
authors: Schmidt
authors: Annette
authors: A
authors: Altmann
authors: Gabriel A
authors: GA
authors: Bonaterra
authors: Antonia
authors: A
authors: Dimitrakopoulou-Strauss
authors: Ludwig G
authors: LG
authors: Strauss
authors: Michael
authors: M
authors: Eisenhut
authors: Ralf
authors: R
authors: Kinscherf
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000378:metabolism*; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D019788:Fluorodeoxyglucose F18; D005947:Glucose
references: Oncol Res. 1996;8(3):111-20
references: 8823807
references: J Clin Oncol. 2002 Sep 15;20(18):3792-803
references: 12228199
references: J Nucl Med. 1993 May;34(5):773-9
references: 8478710
references: J Immunol. 1993 Oct 15;151(8):4248-57
references: 7691942
references: J Exp Med. 2005 Feb 7;201(3):473-84
references: 15699076
references: Eur J Nucl Med. 2001 Apr;28(4):418-25
references: 11357491
references: Cancer Cell. 2005 Oct;8(4):311-21
references: 16226706
references: Clin Cancer Res. 2005 Mar 15;11(6):2132-40
references: 15788658
references: Nucl Med Biol. 1994 Aug;21(6):827-34
references: 9234332
references: J Biol Chem. 2001 Dec 14;276(50):47202-11
references: 11577081
references: Eur J Nucl Med Mol Imaging. 2004 Jan;31(1):5-12
references: 14551748
references: Cancer Res. 2000 Aug 1;60(15):4152-60
references: 10945623
references: J Nucl Med. 1997 Nov;38(11):1818-23
references: 9374364
references: J Nucl Med. 1996 Jun;37(6):931-8
references: 8683314
references: Cancer. 1993 Nov 15;72(10):2979-85
references: 8221565
references: J Nucl Med. 2006 Sep;47(9):1506-14
references: 16954560
references: J Biol Chem. 1997 Mar 21;272(12):7602-7
references: 9065414
references: Cancer Res. 1989 Aug 15;49(16):4452-4
references: 2501025
references: Gene Ther. 1998 Jul;5(7):880-7
references: 9813658
references: J Nucl Med. 2006 Mar;47(3):543-51
references: 16513625
references: J Hepatol. 2004 Jan;40(1):117-23
references: 14672622
references: Int J Cancer. 2006 Jun 15;118(12):2930-5
references: 16395704
references: J Biol Chem. 2000 Dec 8;275(49):38885-90
references: 10986281
references: Biochem Biophys Res Commun. 1993 Feb 15;190(3):881-7
references: 8439337
references: Nucl Med Commun. 2005 Apr;26(4):315-21
references: 15753790
references: Mol Cell Biol. 1987 Jun;7(6):2112-8
references: 2439902
references: Arch Neurol. 1989 Dec;46(12 ):1302-7
references: 2556096
references: Int J Oncol. 2006 May;28(5):1081-8
references: 16596223
references: J Nucl Med. 1991 Aug;32(8):1485-90
references: 1714497
references: J Nucl Med. 1997 Aug;38(8):1215-21
references: 9255154
references: Strahlenther Onkol. 2005 Aug;181(8):507-14
references: 16044218
references: Exp Cell Res. 2005 Nov 1;310(2):370-82
references: 16157329
references: Eur J Nucl Med. 2001 Nov;28(11):1690-6
references: 11702112
references: Lancet Oncol. 2005 May;6(5):266
references: 15889502
references: J Biol Chem. 2003 Apr 25;278(17):15333-40
references: 12566445
references: FASEB J. 1990 Apr 1;4(6):1634-7
references: 2156742
references: Cancer Res. 2005 Jan 15;65(2):613-21
references: 15695406
references: Science. 1987 Mar 20;235(4795):1492-5
references: 3103217
references: J Clin Oncol. 2002 Jan 15;20(2):379-87
references: 11786564
references: Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2525-9
references: 1706526
references: Genes Cells. 2004 Jun;9(6):591-600
references: 15189451
references: Biochem J. 2002 Mar 1;362(Pt 2):273-9
references: 11853534
references: FASEB J. 2006 Feb;20(2):334-6
references: 16371425
references: Mol Med. 2002 Jul;8(7):337-46
references: 12393931
references: J Cancer Res Clin Oncol. 1998 Jan;124(1):27-30
references: 9498831
references: J Nucl Med. 1992 Nov;33(11):1981-7
references: 1432159
references: Ann N Y Acad Sci. 2004 Jun;1019:228-31
references: 15247020