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Horm Metab Res 2012; 44(06): 436-441
DOI: 10.1055/s-0031-1301301
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Reversed Glucose and Fatty Acids Transporter Expression in Human Endometrial Cancer

P. Knapp
1   Department of Gynecology, Medical University of Białystok, Białystok, Poland
,
A. Chabowski
2   Department of Physiology, Medical University of Białystok, Białystok, Poland
,
D. Harasiuk
2   Department of Physiology, Medical University of Białystok, Białystok, Poland
,
J. Górski
2   Department of Physiology, Medical University of Białystok, Białystok, Poland
› Author Affiliations
Further Information

Publication History

received 30 June 2011

accepted 22 December 2011

Publication Date:
20 February 2012 (online)

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Abstract

Cancer cells exhibit accelerated rates of metabolism favoring glucose over fatty acid (FA) utilization. For both energy substrates, protein-mediated transport plays an essential role in facilitating glucose or FA movement across plasma membrane into the cells. Scarce data exist regarding the expression of glucose and/or FA transporter in cancer tissue. Therefore, we examined glucose (GLUT-1, GLUT-3, GLUT-4) and FA (FAT/CD36, FABPpm, FATP-1) transporter expressions at the protein and post-transcript (mRNA) levels in 35 endometrial carcinomas (G1, type endometrioid, FIGO I) and compared them with normal endometrial mucosa (n=10). Endometrial cancer tissue had significantly greater protein expression of GLUT-1, GLUT-3, and GLUT-4 (+ 40%; + 20%; + 24%; p<0.05, respectively) and, conversely, lower fatty acid (FAT/CD36 and FATP-1) transporter expression ( − 25%; p<0.05 and  − 15%, p>0.05 respectively). Interestingly, mRNA content closely mirrors the changes, but only for glucose transporters and not fatty acid transporters. These results suggest the presence of metabolic switch of energy utilization in endometrial cancers favoring glucose consumption as the major source of energy.

Key words

FAT/CD36 - FABPpm - GLUT-1 - GLUT-3 - GLUT-4 - endometrial cancer
 

  • References

  • 1 Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics. Cancer J Clin 2008; 58: 71-96
    CrossrefPubMedGoogle Scholar
  • 2 Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15: 10-17
    CrossrefPubMedGoogle Scholar
  • 3 Lodish H, Berk A, Zipursky SL. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000
    Google Scholar
  • 4 Wooda St, Trayhurna P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 2003; 89: 3-9
    PubMedGoogle Scholar
  • 5 Hamilton JA. New insights into the roles of proteins and lipids in membrane transport of fatty acids. Prostaglandins Leukot Essent Fatty Acids 2007; 77: 355-361
    CrossrefPubMedGoogle Scholar
  • 6 Bonen A, Chabowski A, Luiken JJ, Glatz JF. Is membrane transport of FFA mediated by lipid, protein, or both? Mechanisms and regulation of protein-mediated cellular fatty acid uptake: molecular, biochemical, and physiological evidence. Physiology (Bethesda) 2007; 22: 15-29
    PubMedGoogle Scholar
  • 7 Schaap FG, Hamers L, Van der Vusse GJ, Glatz JFC. Molecular cloning of fatty acid transport protein cDAN from rat. Biochim Biophys Acta 1997; 1354: 29-34
    CrossrefPubMedGoogle Scholar
  • 8 Diede HE, Rodilla-Sala E, Gunawan J, Manns M, Stremmel W. Identification and characterization of a monoclonal antibody to the membrane fatty acid binding protein. Biochim Biophys Acta 1992; 1125: 13-20
    CrossrefPubMedGoogle Scholar
  • 9 Abumrad NA, El-Maghrabi MR, Amri E-Z, Lopez E, Grimaldi P. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. J Biol Chem 1993; 268: 17665-17668
    PubMedGoogle Scholar
  • 10 von Wolff M, Ursel S, Hahn U, Steldinger R, Strowitzki T. Glucose transporter proteins (GLUT) in human endometrium: expression, regulation, and function throughout the menstrual cycle and in early pregnancy. J Clin Endocrinol Metab 2003; 88: 3885-3892
    CrossrefPubMedGoogle Scholar
  • 11 Duttaroy AK. Transport of fatty acids across the human placenta: a review. Prog Lipid Res 2009; 48: 52-61
    CrossrefPubMedGoogle Scholar
  • 12 Warburg O. On the origin of cancer cells. Science 1956; 123: 309-314
    CrossrefPubMedGoogle Scholar
  • 13 Ristow M. Oxidative metabolism in cancer growth. Curr Opin Clin Nutr Metab Care 2006; 9: 339-345
    CrossrefPubMedGoogle Scholar
  • 14 DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008; 7: 11-20
    CrossrefPubMedGoogle Scholar
  • 15 Holm E, Hagmüller E, Staedt U, Schlickeiser G, Günther HJ, Leweling H, Tokus M, Kollmar HB. Substrate balances across colonic carcinomas in humans. Cancer Res 1995; 55: 1373-1378
    PubMedGoogle Scholar
  • 16 Ogunbiyi OA, Flanagan FL, Dehdashti F, Siegel BA, Trask DD, Birnbaum EH, Fleshman JW, Read TE, Philpott GW, Kodner IJ. Staging of esophageal cancer with 18F-fluorodeoxyglucose positron emission tomography. Am J Roentgenol 1997; 168: 417-424
    PubMedGoogle Scholar
  • 17 Yun J, Rago C, Cheong I, Pagliarini R, Angenendt P, Rajagopalan H, Schmidt K, Willson JK, Markowitz S, Zhou S, Diaz Jr LA, Velculescu VE, Lengauer C, Kinzler KW, Vogelstein B, Papadopoulos N. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 2009; 325 (5947) 1555-1559
    CrossrefPubMedGoogle Scholar
  • 18 Villavicencio A, Bacallao K, Avellaira C, Gabler F, Fuentes A, Vega M. Androgen and estrogen receptors and co-regulators levels in endometria from patients with polycystic ovarian syndrome with and without endometrial hyperplasia. Gynecol Oncol 2006; 103: 307-314
    CrossrefPubMedGoogle Scholar
  • 19 Avellaira C, Villavicencio A, Bacallao K, Gabler F, Wells P, Romero C, Vega M. Expression of molecules associated with tissue homeostasis in secretory endometria from untreated women with polycystic ovary syndrome. Hum Reprod 2006; 21: 3116-3121
    CrossrefPubMedGoogle Scholar
  • 20 Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29: 2003-2007
    CrossrefPubMedGoogle Scholar
  • 21 Ortega AD, Sánchez-Aragó M, Giner-Sánchez D, Sánchez-Cenizo L, Willers I, Cuezva JM. Glucose avidity of carcinomas. Cancer Lett 2009; 276: 125-135
    CrossrefPubMedGoogle Scholar
  • 22 Goldman NA, Katz EB, Glenn AS, Weldon RH, Jones JG, Lynch U, Fezzari MJ, Runowicz CD, Goldberg GL, Charron MJ. GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma. Mod Pathol 2006; 19: 1429-1436
    PubMedGoogle Scholar
  • 23 Medina RA, Meneses AM, Vera JC, Gúzman C, Nualart F, Rodriguez F, de los Angeles Garcia M, Kato S, Espinoza N, Monsó C, Carvajal A, Pinto M, Owen GI. Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells. J Endocrinol 2004; 182: 467-478
    CrossrefPubMedGoogle Scholar
  • 24 Airley RE, Mobasheri A. Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy 2007; 53: 233-256
    CrossrefPubMedGoogle Scholar
  • 25 Watson RT, Pessin JE. Intracellular organization of insulin signaling and GLUT4 translocation. Recent Prog Horm Res 2001; 56: 175-193
    CrossrefPubMedGoogle Scholar
  • 26 Fornes R, Ormazabal P, Rosas C, Gabler F, Vantman D, Romero C, Vega M. Changes in the expression of insulin signaling pathway molecules in endometria from polycystic ovary syndrome women with or without hyperinsulinemia. Mol Med 2010; 16: 129-136
    CrossrefPubMedGoogle Scholar
  • 27 Gojnic M, Dugalic V, Brankovic M, Stojanovic I, Acimovic M, Vasiljevic B. Is insulin-dependent diabetes and obesity a predisposition for endometrial and pancreatic carcinoma?. Clin Exp Obstet Gynecol 2010; 37: 152-154
    PubMedGoogle Scholar
  • 28 Rosato V, Zucchetto A, Bosetti C, Dal Maso L, Montella M, Pelucchi C, Negri E, Franceschi S, La Vecchia C. Metabolic syndrome and endometrial cancer risk. Ann Oncol 2011; 22: 884-889
    CrossrefPubMedGoogle Scholar
  • 29 Koch M, Hussein F, Woeste A, Gründker C, Frontzek K, Emons G, Hawighorst T. CD36-mediated activation of endothelial cell apoptosis by an N-terminal recombinant fragment of thrombospondin-2 inhibits breast cancer growth and metastasis in vivo. Breast Cancer Res Treat 2010; 128: 565-572
    PubMedGoogle Scholar
  • 30 Yan J, Gong Y, Wang G, Gong Y, Burczynski FJ. Regulation of liver fatty acid binding protein expression by clofibrate in hepatoma cells. Biochem Cell Biol 2010; 88: 957-967
    CrossrefPubMedGoogle Scholar
  • 31 Kuemmerle NB, Rysman E, Lombardo PS, Flanagan AJ, Lipe BC, Wells WA, Pettus JR, Froehlich HM, Memoli VA, Morganelli PM, Swinnen JV, Timmerman LA, Chaychi L, Fricano CJ, Eisenberg BL, Coleman WB, Kinlaw WB. Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Mol Cancer Ther 2011; 10: 427-436
    CrossrefPubMedGoogle Scholar
  • 32 Blask DE, Brainard GC, Dauchy RT, Hanifin JP, Davidson LK, Krause JA, Sauer LA, Rivera-Bermudez MA, Dubocovich ML, Jasser SA, Lynch DT, Rollag MD, Zalatan F. Melatonin inhibition of cancer growth in vivo involves suppression of tumor fatty acid metabolism via melatonin receptor-mediated signal transduction events. Cancer Res 1999; 59: 4693-4701
    PubMedGoogle Scholar
  • 33 Schimanski S, Wild PJ, Treeck O, Horn F, Sigruener A, Rudolph C, Blaszyk H, Klinkhammer-Schalke M, Ortmann O, Hartmann A, Schmitz G. Expression of the lipid transporters ABCA3 and ABCA1 is diminished in human breast cancer tissue. Horm Metab Res 2010; 42: 102-109
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Shirato K, Nakajima K, Korekane H, Takamatsu S, Gao C, Angata T, Ohtsubo K, Taniguchi N. Hypoxic regulation of glycosylation via the N-acetylglucosamine cycle. J Clin Biochem Nutr 2011; 48: 20-25
    PubMedGoogle Scholar
  • 35 Gayther SA, Barski P, Batley SJ, Li L, de Foy KA, Cohen SN, Ponder BA, Caldas C. Aberrant splicing of the TSG101 and FHIT genes occurs frequently in multiple malignancies and in normal tissues and mimics alterations previously described in tumours. Oncogene 1997; 15: 2119-2126
    CrossrefPubMedGoogle Scholar
  • 36 Lee MP, Feinberg AP. Aberrant splicing but not mutations of TSG101 in human breast cancer. Cancer Res 1997; 57: 3131-3134
    PubMedGoogle Scholar
  • 37 Chabowski A, Górski J, Bonen A. Regulation of fatty acid transport: from transcriptional to posttranscriptional effects. Naunyn Schmiedebergs Arch Pharmacol 2006; 373: 259-263
    CrossrefPubMedGoogle Scholar
  • 38 Dutta-Roy AK. Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta. Am J Clin Nutr 2000; 71 (1 Suppl) 315S-322S
    PubMedGoogle Scholar