RSS-Feed abonnieren
DOI: 10.1055/s-0032-1312922
The Role of Bile Acids in the Neoplastic Progression of Barrett’s Esophagus – A Short Representative Overview
Die Rolle der Gallensäuren in der neoplastischen Progression des Barrett-Ösophagus – eine repräsentative ÜbersichtPublikationsverlauf
07. Februar 2012
17. Mai 2012
Publikationsdatum:
10. September 2012 (online)
Abstract
Barrett’s esophagus (BE) is an intestinal metaplasia of the distal esophagus in which squamous cells are replaced by a columnar epithelium. It is considered as a premalignant lesion, which can lead to esophageal adenocarcinoma, a very aggressive type of cancer, and can often be found in patients with gastro-esophageal reflux disease (GERD). In spite of the widespread use of acid-suppressing therapy with proton pump inhibitors, the incidence of adenocarcinoma has been steadily rising during the last 30 years. So, it can strongly be suggested that refluxed material other than acid might contribute to the progression of cancer within Barrett’s esophagus. Along with gastric acid, bile acids enter the esophagus during an episode of reflux, and bile acids may be important in carcinogenesis. In their refluxates, patients with GERD and BE show high concentrations of the hydrophobic bile salt deoxycholic acid (DCA), which has cytotoxic effects and is able to induce DNA damage in different cell types. Other bile acids, like the hydrophilic urodeoxycholic acid (UDCA), have been therapeutically used to treat cholestatic liver diseases and to prevent colon carcinoma. This article reviews the effects of bile acids and points out new perceptions in the progression of Barrett’s-associated carcinogenesis.
Zusammenfassung
Der Barrett-Ösophagus (BE) stellt eine intestinale Metaplasie des distalen Ösophagus dar, indem Plattenepithelzellen durch Zylinderepithel ersetzt werden. Diese Veränderung ist als prämaligne Läsion zu betrachten, die zum Adenokarzinom des Ösophagus führen kann, einer sehr aggressiven malignen Neoplasie, die nicht selten bei Patienten mit vorbestehender gastroösophagealer Refluxerkrankung (GERD) gefunden wird. Trotz eines weitverbreiteten Gebrauchs an säureblockierender Therapie mit Protonenpumpeninhibitoren (PPI) hat die Inzidenz des Adenokarzinoms während der letzten 30 Jahre ständig zugenommen. Daher kann recht sicher angenommen werden, dass auch „nicht saures“ Refluxmaterial zur Krebsentstehung im Barrett-Ösophagus beitragen könnte. Neben der Magensäure benetzen auch Gallensäuren die Speiseröhre während einer Refluxepisode, was nahelegt, dass auch Gallensäuren in der Karzinogenese von Bedeutung sein könnten. In ihren Refluxaten weisen Patienten mit GERD und BE außerdem hohe Konzentrationen der Gallensalze, besonders der hydrophoben Desoxycholsäure (DCA) auf, die zytotoxische Effekte auslöst und DNA-Schäden an diversen Zelltypen induzieren kann. Andere Gallensalze der eher hydrophilen Urodesoxycholsäure (UDCA) sind bereits therapeutisch angewandt worden, um cholestatische Lebererkrankungen zu behandeln und dem Kolonkarzinom vorzubeugen. Dieser Artikel gibt einen kurzen repräsentativen Überblick zum Effekt der Gallensäuren und führt neue Betrachtungsansätze in der Barrett-assoziierten Karzinogenese aus.
-
References
- 1 Quaroni L, Zhao R, Casson AG. Shining light on Barrett’s esophagus. Expert Rev Gastroenterol Hepatol 2009; 3: 577-580
- 2 El Rifai W, Powell SM. Molecular biology of gastric cancer. Semin Radiat Oncol 2002; 12: 128-140
- 3 Zhang HY, Spechler SJ, Souza RF. Esophageal adenocarcinoma arising in Barrett esophagus. Cancer Lett 2009; 275: 170-177
- 4 Pascu O, Lencu M. Barrett’s Esophagus. Romanian J Gastroenterol 2004; 13: 219-222
- 5 Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005; 97: 142-146
- 6 Spechler SJ, Sharma P, Souza RF et al. American Gastroenterological Association Medical Position Statement of the Management of Barrett’s Esophagus. Gastroenterology 2011; 140: 1084-1091
- 7 Souza RF, Spechler SJ. Concepts in the prevention of adenocarcinoma of the distal esophagus and proximal stomach. CA Cancer J Clin 2005; 55: 334-351
- 8 Eloubeidi MA, Mason AC, Desmond RA et al. Temporal trends (1973–1997) in survival of patients with esophageal adenocarcinoma in the United States: a glimmer of hope?. Am J Gastroenterol 2003; 98: 1627-1633
- 9 Hvid-Jensen F, Pedersen L, Drewes AM et al. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med 2011; 365: 1375-1383
- 10 Wang X, Ouyang H, Yamamoto Y et al. Residual embryonic cells as precursors of a Barrett’s-like metaplasia. Cell 2011; 145: 1023-1035
- 11 Tosh D, Slack JM. How cells change their phenotype. Nat Rev Mol Cell Biol 2002; 3: 187-194
- 12 Souza RF, Krishnan K, Spechler SJ. Acid, bile, and CDX: the ABCs of making Barrett’s metaplasia. Am J Physiol Gastrointest Liver Physiol 2008; 295: G211-G218
- 13 Hutchinson L, Stenstrom B, Chen D et al. Human Barrett’s adenocarcinoma of the esophagus, associated myofibroblasts, and endothelium can arise from bone marrow-derived cells after allogeneic stem cell transplant. Stem Cells Dev 2011; 20: 11-17
- 14 Fitzgerald RC, Lascar R, Triadafilopoulos G. Review article: Barrett’s oesophagus, dysplasia and pharmacologic acid suppression. Aliment Pharmacol Ther 2001; 15: 269-276
- 15 Tobey NA, Hosseini SS, Caymaz-Bor C et al. The role of pepsin in acid injury to esophageal epithelium. Am J Gastroenterol 2001; 96: 3062-3070
- 16 Ismail-Beigi F, Horton PF, Pope CE. Histological consequences of gastroesophageal reflux in man. Gastroenterology 1970; 58: 163-174
- 17 Orlando RC. Pathophysiology of gastroesophageal reflux disease. J Clin Gastroenterol 2008; 42: 584-588
- 18 Souza RF, Huo X, Mittal V et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology 2009; 137: 1776-1784
- 19 Rieder F, Biancani P, Harnett K et al. Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis. Am J Physiol Gastrointest Liver Physiol 2010; 298: G571-G581
- 20 Dobbagh K, Takeyama K, Lee H et al. IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo. J Immunol 1999; 162: 6233-6237
- 21 Yoshida N. Inflammation and Oxidative Stress in Gastroesophageal Reflux Disease. J Clin Biochem Nutr 2007; 40: 13-23
- 22 Salminen JT, Tuominen JA, Rämö OJ et al. Oesophageal acid exposure: higher in Barrett’s oesophagus than in reflux oesophagitis. Ann Med 1999; 31: 46-50
- 23 Katz PO. The role of non-acid reflux in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2000; 14: 1539-1551
- 24 Perez MJ, Briz O. Bile-acid-induced cell injury and protection. World J Gastroenterol 2009; 15: 1677-1689
- 25 Frazzoni M, Conigliaro R, Melotti G. Weakly acidic refluxes have a major role in the pathogenesis of proton pump inhibitor-resistant reflux oesophagitis. Aliment Pharmacol Ther 2011; 33: 601-606
- 26 Nehra D, Howell P, Williams CP et al. Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity. Gut 1999; 44: 598-602
- 27 Mahmoud NN, Dannenberg AJ, Bilinski RT et al. Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis. Carcinogenesis 1999; 20: 299-303
- 28 Kauer WK, Peters JH, DeMeester TR et al. Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re-emphasized. Ann Surg 1995; 222: 525-531
- 29 Billington D, Evans CE, Godfrey PP et al. Effects of bile salts on the plasma membranes of isolated rat hepatocytes. Biochem J 1980; 188: 321-327
- 30 Gores GJ, Miyoshi H, Botla R et al. Induction of the mitochondrial permeability transition as a mechanism of liver injury during cholestasis: a role for mitochondrial proteases. Biochem Biophys Acta 1998; 1366: 167-175
- 31 Vaezi MF, Richter JE. Duodenogastro-oesophageal reflux. Baillieres Best Pract Res Clin Gastroenterol 2000; 14: 719-729
- 32 Chen X, Yang CS. Esophageal adenocarcinoma: a review and perspectives on the mechanism of carcinogenesis and chemoprevention. Carcinogenesis 2001; 22: 1119-1129
- 33 Crowley-Weber CL, Payne CM, Gleason-Guzman M et al. Development and molecular characterisation of HCT-116 cell lines resistant to the tumor promoter and multiple stress-inducer, deoxycholate. Carcinogenesis 2008; 23: 2063-2080
- 34 Hellerbrand C, Hoeger S, Muelbauer M et al. Bile acids induce proinflammatory cytokine expression in activated hepatic stellate cells via NFKB activation. Hepatology 2000; 32: 156
- 35 Burnat G, Majka J, Konturek PC. Bile acids are multifunctional modulators of the Barrett’s carcinogenesis. J Physiol Pharmacol 2010; 61: 185-192
- 36 Scates DK, Venitt S, Phillips RK et al. High pH reduces DNA damage caused by bile from patients with familial adenomatous polyposis – antacids may attenuate duodenal polyposis. Gut 1995; 36: 918-921
- 37 Booth LA, Gilmore IT, Bilton RF. Secondary bile acid induced DNA damage in HT29 cells: are free radicals involved?. Free Radic Res 1997; 26: 135-144
- 38 Hatada EN, Nieters A, Wulczyn FG et al. The ankyrin repeat domains of the NF-kappa B precursor p105 and the protooncogene bcl-3 act as specific inhibitors of NF-kappa B DNA binding. Proc Natl Acad Sci USA 1992; 89: 2489-2493
- 39 Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell 2002; 109: 81-96
- 40 Ravi R, Bedi A. NF-kappaB in cancer – a friend turned foe. Drug Resist Updat 2004; 7: 53-67
- 41 Van Waes C. Nuclear factor-κB in development, prevention, and therapy of Cancer. Clin Cancer Res 2007; 13: 1076-1082
- 42 Karin M, Cao Y, Greten FR et al. NF-κB in cancer: from innocent bystander to major culprit. Nature Rev Cancer 2002; 2: 301-310
- 43 Dvorakova K, Payne CM, Ramsey L et al. Apoptosis resistance in Barrett’s esophagus: ex vivo bioassay of live stressed tissues. Am J Gastroenterol 2005; 100: 424-431
- 44 Katada N, Hinder RA, Smyrk TC et al. Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett esophagus. Arch Surg 1997; 132: 728-733
- 45 Van de Meeberg PC, van Erpecum KJ, van Berge-Henegouwen GP. Therapy with ursodeoxycholic acid in cholestatic liver disease. Scand J Gastroenterol 1993; 200: 15-20
- 46 Stiehl A. Treatment of cholestatic liver diseases; the role of ursodeoxycholic acid. Z Gastroenterol 1992; 30: 743-747
- 47 Rodrigues CM, Fan G, Wong PY et al. Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production. Mol Med 1998; 4: 165-178
- 48 Croog VJ, Ullman TA, Itzkowitz SH. Chemoprevention of colorectal cancer in ulcerative colitis. Int J Colorectal Dis 2003; 18: 392-400
- 49 Huo X, Juergens S, Zhang X et al. Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett’s epithelial cells. Am J Physiol Gastrointest Liver Physiol 2011; 301: G278-G286
- 50 Hormi-Carver K, Zhang X, Zhang HY et al. Unlike esophageal squamous cells, Barrett’s epithelial cells resist apoptosis by activating the nuclear factor-kappaB pathway. Cancer Res 2009; 69: 672-677
- 51 Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70
- 52 Jenkins GJ, Cronin J, Alhamdani A et al. The bile acid deoxycholic acid has a non-linear dose response for DNA damage and possibly NF-kappaB activation in oesophageal cells, with a mechanism of action involving ROS. Mutagenesis 2008; 23: 3399-3405
- 53 Jenkins GJ, Harries K, Doak SH et al. The bile acid deoxycholic acid (DCA) at neutral pH activates NF-kappaB and induces IL-8 expression in oesophageal cells in vitro. Carcinogenesis 2004; 25: 317-323
- 54 Armstrong D, Rytina ER, Murphy GM et al. Gastric mucosal toxicity of duodenal juice constituents in the rat. Acute studies using ex vivo rat gastric chamber model. Dig Dis Sci 1994; 39: 327-339
- 55 Lee DK, Park SY, Baik SK et al. Deoxycholic acid-induced signal transduction in HT-29 cells: role of NF-kappa B and interleukin-8. Korean J Gastroenterol 2004; 43: 176-185
- 56 Amaral JD, Viana RJ, Ramalho RM et al. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res 2009; 50: 1721-1734
- 57 Schoemaker MH, Gommans WM, Conde de la Rosa L et al. Resistance of rat hepatocytes against bile acid-induced apoptosis in cholestatic liver injury is due to nuclear factor-kappa B activation. J Hepatol 2003; 39: 153-161
- 58 Beuers U, Boyer JL, Paumgartner G. Ursodeoxycholic acid in cholestasis: potential mechanisms of action and therapeutic applications. Hepatology 1998; 28: 1449-1453
- 59 Rodrigues CM, Fan G, Ma X et al. A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest 1998; 101: 2790-2799
- 60 Tung BY, Emond MJ, Haggitt RC et al. Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Ann Intern Med 2001; 134: 89-95
- 61 Serfaty L, De Leusse A, Rosmorduc O et al. Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Hepatology 2003; 38: 203-209
- 62 Im E, Martinez JD. Ursodeoxycholic acid (UDCA) can inhibit deoxycholic acid (DCA)-induced apoptosis via modulation of EGFR/Raf-1/ERK signaling in human colon cancer cells. J Nutr 2004; 134: 483-486
- 63 Rizvi S, Demars CJ, Comba A et al. Combinatorial chemoprevention reveals a novel smoothened-independent role of GLI1 in esophageal carcinogenesis. Cancer Res 2010; 70: 6787-6796
- 64 Vaezi MF, Richter JE. Role of acid and duodenogastroesophageal reflux in gastroesophageal reflux disease. Gastroenterology 1996; 111: 1192-1199
- 65 Raj A, Jankowski J. Acid suppression and chemoprevention in Barrett’s oesophagus. Dig Dis 2004; 22: 171-180
- 66 Abrams JA. Chemoprevention of esophageal adenocarcinoma. Therap Adv Gastroenterol 2008; 1: 7-18
- 67 Mehta SP, Body AP, Cook I et al. Effect of n-3 polyunsaturated fatty acids on Barrett’s epithelium in human lower esophagus. Am J Clin Nutr 2008; 87: 949-956