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)

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.

 
  • 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
  • 2 Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15: 10-17
  • 3 Lodish H, Berk A, Zipursky SL. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000
  • 4 Wooda St, Trayhurna P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 2003; 89: 3-9
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 11 Duttaroy AK. Transport of fatty acids across the human placenta: a review. Prog Lipid Res 2009; 48: 52-61
  • 12 Warburg O. On the origin of cancer cells. Science 1956; 123: 309-314
  • 13 Ristow M. Oxidative metabolism in cancer growth. Curr Opin Clin Nutr Metab Care 2006; 9: 339-345
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 20 Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29: 2003-2007
  • 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
  • 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
  • 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
  • 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
  • 25 Watson RT, Pessin JE. Intracellular organization of insulin signaling and GLUT4 translocation. Recent Prog Horm Res 2001; 56: 175-193
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 36 Lee MP, Feinberg AP. Aberrant splicing but not mutations of TSG101 in human breast cancer. Cancer Res 1997; 57: 3131-3134
  • 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
  • 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