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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2012

01-11-2012 | Review Article

Chemotherapy-induced gut toxicity: are alterations to intestinal tight junctions pivotal?

Authors: Hannah R. Wardill, Joanne M. Bowen, Rachel J. Gibson

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2012

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Abstract

Chemotherapy-induced gut toxicity (CIGT) is a frequent, debilitating and dose-limiting side effect of anti-cancer cytotoxic therapies. Despite much research, many of the underlying mechanisms remain poorly understood. Recently, there has been renewed interest in the role that intestinal permeability and tight junctions play in the pathogenesis of chemotherapy-induced gut toxicity. Tight junctions have been linked with many of the known hall marks of toxicity including pro-inflammatory cytokines and pathogenic bacteria. In this critical review, we highlight the research literature addressing modifications in tight junctions following chemotherapy administration and how tight junctions may be implicated in the pathophysiology of CIGT.
Literature
1.
2.
Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE, Migliorati CA, McGuire DB, Hutchins RD, Peterson DE (2007) Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 109(5):820–831PubMedCrossRef
3.
Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB (2003) The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 98(7):1531–1539PubMedCrossRef
4.
Keefe DM, Cummins AG, Dale BM, Kotasek D, Robb TA, Sage RE (1997) Effect of high-dose chemotherapy on intestinal permeability in humans. Clin Sci 92(4):385–389PubMed
5.
Sonis ST (2004) Oral mucositis in cancer therapy. J Support Oncol 2(6 Suppl 3):3–8PubMed
6.
Sonis ST (2004) A biological approach to mucositis. J Support Oncol 2(1):21–32 discussion 35–26PubMed
7.
Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, Elting LS, Fox PC, Cooksley C, Sonis ST (2004) Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 100(9 Suppl):2026–2046PubMedCrossRef
8.
Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100(9 Suppl):1995–2025PubMedCrossRef
9.
Logan RM, Gibson RJ, Bowen JM, Stringer AM, Sonis ST, Keefe DM (2008) Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis. Cancer Chemother Pharmacol 62(1):33–41PubMedCrossRef
10.
Clarke JM, Pelton NC, Bajka BH, Howarth GS, Read LC, Butler RN (2006) Use of the 13C-sucrose breath test to assess chemotherapy-induced small intestinal mucositis in the rat. Cancer Biol Ther 5(1):34–38PubMedCrossRef
11.
Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST, Keefe DM (2008) Serum levels of NFkappaB and pro-inflammatory cytokines following administration of mucotoxic drugs. Cancer Biol Ther 7(7):1139–1145PubMedCrossRef
12.
Stringer AM, Gibson RJ, Bowen JM, Logan RM, Yeoh AS, Keefe DM (2007) Chemotherapy-induced mucositis: the role of gastrointestinal microflora and mucins in the luminal environment. J Support Oncol 5(6):259–267PubMed
13.
Ma TY, Iwamoto GK, Hoa NT, Akotia V, Pedram A, Boivin MA, Said HM (2004) TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol 286(3):G367–G376PubMedCrossRef
14.
Logan RM, Stringer AM, Bowen JM, Yeoh AS, Gibson RJ, Sonis ST, Keefe DM (2007) The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev 33(5):448–460PubMedCrossRef
15.
Philpott DJ, McKay DM, Sherman PM, Perdue MH (1996) Infection of T84 cells with enteropathogenic Escherichia coli alters barrier and transport functions. Am Journal Physiol 270(4 Pt 1):G634–G645
16.
Spitz J, Yuhan R, Koutsouris A, Blatt C, Alverdy J, Hecht G (1995) Enteropathogenic Escherichia coli adherence to intestinal epithelial monolayers diminishes barrier function. Am J Physiol 268(2 Pt 1):G374–G379PubMed
17.
Walsh-Reitz MM, Huang EF, Musch MW, Chang EB, Martin TE, Kartha S, Toback FG (2005) AMP-18 protects barrier function of colonic epithelial cells: role of tight junction proteins. Am J Physiol Gastrointest Liver Physiol 289(1):G163–G171PubMedCrossRef
18.
Al-Sadi R, Ye D, Dokladny K, Ma TY (2008) Mechanism of IL-1beta-induced increase in intestinal epithelial tight junction permeability. J Immunol 180(8):5653–5661PubMed
19.
Bertiaux-Vandaele N, Youmba SB, Belmonte L, Lecleire S, Antonietti M, Gourcerol G, Leroi AM, Dechelotte P, Menard JF, Ducrotte P, Coeffier M (2011) The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol 106(12):2165–2173PubMedCrossRef
20.
Groschwitz KR, Hogan SP (2009) Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol 124(1):3–20 quiz 21–22PubMedCrossRef
21.
Blijlevens NM, Donnelly JP, de Pauw BE (2005) Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant. Bone Marrow Transplant 35(7):707–711PubMedCrossRef
22.
Blijlevens NM, Van’t Land B, Donnelly JP, M’Rabet L, de Pauw BE (2004) Measuring mucosal damage induced by cytotoxic therapy. Support Care Cancer 12(4):227–233PubMedCrossRef
23.
Daniele B, Secondulfo M, De Vivo R, Pignata S, De Magistris L, Delrio P, Palaia R, Barletta E, Tambaro R, Carratu R (2001) Effect of chemotherapy with 5-fluorouracil on intestinal permeability and absorption in patients with advanced colorectal cancer. J Clin Gastroenterol 32(3):228–230PubMedCrossRef
24.
Fazeny-Dorner B, Veitl M, Wenzel C, Brodowicz T, Zielinski C, Muhm M, Vogelsang H, Marosi C (2002) Alterations in intestinal permeability following the intensified polydrug-chemotherapy IFADIC (ifosfamide, Adriamycin, dacarbazine). Cancer Chemother Pharmacol 49(4):294–298PubMedCrossRef
25.
Melichar B, Kohout P, Bratova M, Solichova D, Kralickova P, Zadak Z (2001) Intestinal permeability in patients with chemotherapy-induced stomatitis. J Cancer Res Clin Oncol 127(5):314–318PubMedCrossRef
26.
Hollander D (1999) Intestinal permeability, leaky gut, and intestinal disorders. Curr Gastroenterol Rep 1(5):410–416PubMedCrossRef
27.
Gonzalez-Mariscal L, Tapia R, Chamorro D (2008) Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta 1778(3):729–756PubMedCrossRef
28.
Ley RE, Peterson DA, Gordon JI (2006) Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124(4):837–848PubMedCrossRef
29.
Melichar B, Dvorak J, Hyspler R, Zadak Z (2005) Intestinal permeability in the assessment of intestinal toxicity of cytotoxic agents. Chemotherapy 51(6):336–338PubMedCrossRef
30.
Madara JL (1998) Regulation of the movement of solutes across tight junctions. Annu Rev Physiol 60:143–159PubMedCrossRef
31.
Anderson JM, Balda MS, Fanning AS (1993) The structure and regulation of tight junctions. Curr Opin Cell Biol 5(5):772–778PubMedCrossRef
32.
Hollande F, Lee DJ, Choquet A, Roche S, Baldwin GS (2003) Adherens junctions and tight junctions are regulated via different pathways by progastrin in epithelial cells. J Cell Sci 116(Pt 7):1187–1197PubMedCrossRef
33.
Inoko A, Itoh M, Tamura A, Matsuda M, Furuse M, Tsukita S (2003) Expression and distribution of ZO-3, a tight junction MAGUK protein, in mouse tissues. Genes Cells 8(11):837–845PubMedCrossRef
34.
Gottardi CJ, Arpin M, Fanning AS, Louvard D (1996) The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell–cell contacts. Proc Nat Acad Sci USA 93(20):10779–10784PubMedCrossRef
35.
Umeda K, Ikenouchi J, Katahira-Tayama S, Furuse K, Sasaki H, Nakayama M, Matsui T, Tsukita S, Furuse M (2006) ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell 126(4):741–754PubMedCrossRef
36.
Gumbiner B, Lowenkopf T, Apatira D (1991) Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1. Proc Nat Acad Sci USA 88(8):3460–3464PubMedCrossRef
37.
Morita K, Furuse M, Fujimoto K, Tsukita S (1999) Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Nat Acad Sci USA 96(2):511–516PubMedCrossRef
38.
Will C, Fromm M, Muller D (2008) Claudin tight junction proteins: novel aspects in paracellular transport. Perit Dial Int 28(6):577–584PubMed
39.
Poritz LS, Garver KI, Tilberg AF, Koltun WA (2004) Tumor necrosis factor alpha disrupts tight junction assembly. J Surg Res 116(1):14–18PubMedCrossRef
40.
McCarthy KM, Skare IB, Stankewich MC, Furuse M, Tsukita S, Rogers RA, Lynch RD, Schneeberger EE (1996) Occludin is a functional component of the tight junction. J Cell Sci 109(Pt 9):2287–2298PubMed
41.
Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC (2011) Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr 141(5):769–776PubMedCrossRef
42.
Balda MS, Whitney JA, Flores C, Gonzalez S, Cereijido M, Matter K (1996) Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein. J Cell Biol 134(4):1031–1049PubMedCrossRef
43.
Schulzke JD, Gitter AH, Mankertz J, Spiegel S, Seidler U, Amasheh S, Saitou M, Tsukita S, Fromm M (2005) Epithelial transport and barrier function in occludin-deficient mice. Biochim Biophys Acta 1669(1):34–42PubMedCrossRef
44.
Yu AS, McCarthy KM, Francis SA, McCormack JM, Lai J, Rogers RA, Lynch RD, Schneeberger EE (2005) Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells. Am J Physiol Cell Physiol 288(6):C1231–C1241PubMedCrossRef
45.
Suzuki T, Elias BC, Seth A, Shen L, Turner JR, Giorgianni F, Desiderio D, Guntaka R, Rao R (2009) PKC eta regulates occludin phosphorylation and epithelial tight junction integrity. Proc Nat Acad Sci USA 106(1):61–66PubMedCrossRef
46.
Gibson RJ, Bowen JM, Alvarez E, Finnie J, Keefe DM (2007) Establishment of a single-dose irinotecan model of gastrointestinal mucositis. Chemotherapy 53(5):360–369PubMedCrossRef
47.
Ma MK, McLeod HL (2003) Lessons learned from the irinotecan metabolic pathway. Curr Med Chem 10(1):41–49PubMedCrossRef
48.
Gibson RJ, Bowen JM, Inglis MR, Cummins AG, Keefe DM (2003) Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer. J Gastroenterol Hepatol 18(9):1095–1100PubMedCrossRef
49.
Melichar B, Dvorak J, Krcmova L, Hyspler R, Urbanek L, Solichova D (2008) Intestinal permeability and vitamin A absorption in patients with chemotherapy-induced diarrhea. Am J Clin Oncol 31(6):580–584PubMedCrossRef
50.
Nakao T, Nobuhiro K, Komatsu M, Yoshikawa K, Iwata T, Utusnomiya T, Shimada M (2012) Irinotecan injures tight junction and causes bacterial translocation in rat. J Surg Res 173:341–347PubMedCrossRef
51.
Capaldo CT, Nusrat A (2009) Cytokine regulation of tight junctions. Biochim Biophys Acta 1788(4):864–871PubMedCrossRef
52.
Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, Riecken EO, Schulzke JD (1999) Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology 116(2):301–309PubMedCrossRef
53.
Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC, Spiller RC (2006) Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. American J Gastroenterol 101(6):1288–1294CrossRef
54.
Camilleri M, Gorman H (2007) Intestinal permeability and irritable bowel syndrome. Neurogastroenterol Motility 19(7):545–552CrossRef
55.
Marshall JK, Thabane M, Garg AX, Clark W, Meddings J, Collins SM (2004) Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton. Ontario. Aliment Pharmacol Ther 20(11–12):1317–1322PubMedCrossRef
56.
Tibble JA, Sigthorsson G, Foster R, Forgacs I, Bjarnason I (2002) Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology 123(2):450–460PubMedCrossRef
57.
Schulzke JD, Ploeger S, Amasheh M, Fromm A, Zeissig S, Troeger H, Richter J, Bojarski C, Schumann M, Fromm M (2009) Epithelial tight junctions in intestinal inflammation. Ann N Y Acad Sci 1165:294–300PubMedCrossRef
58.
Bruewer M, Luegering A, Kucharzik T, Parkos CA, Madara JL, Hopkins AM, Nusrat A (2003) Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol 171(11):6164–6172PubMed
59.
Chavez AM, Menconi MJ, Hodin RA, Fink MP (1999) Cytokine-induced intestinal epithelial hyperpermeability: role of nitric oxide. Crit Care Med 27(10):2246–2251PubMedCrossRef
60.
Coyne CB, Vanhook MK, Gambling TM, Carson JL, Boucher RC, Johnson LG (2002) Regulation of airway tight junctions by proinflammatory cytokines. Mol Biol Cell 13(9):3218–3234PubMedCrossRef
61.
Mankertz J, Tavalali S, Schmitz H, Mankertz A, Riecken EO, Fromm M, Schulzke JD (2000) Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma. J Cell Sci 113(Pt 11):2085–2090PubMed
62.
Tazuke Y, Drongowski RA, Teitelbaum DH, Coran AG (2003) Interleukin-6 changes tight junction permeability and intracellular phospholipid content in a human enterocyte cell culture model. Pediatr Surg Int 19(5):321–325PubMedCrossRef
63.
Williams DA (2001) Inflammatory cytokines and mucosal injury. J Nat Cancer Inst Monogr 29:26–30CrossRef
64.
Edelblum KL, Turner JR (2009) The tight junction in inflammatory disease: communication breakdown. Curr Opin Pharmacol 9(6):715–720PubMedCrossRef
65.
Ma TY, Boivin MA, Ye D, Pedram A, Said HM (2005) Mechanism of TNF-{alpha} modulation of Caco-2 intestinal epithelial tight junction barrier: role of myosin light-chain kinase protein expression. Am J Physiol Gastrointest Liver Physiol 288(3):G422–G430PubMedCrossRef
66.
Melo ML, Brito GA, Soares RC, Carvalho SB, Silva JV, Soares PM, Vale ML, Souza MH, Cunha FQ, Ribeiro RA (2008) Role of cytokines (TNF-alpha, IL-1beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide. Cancer Chemother Pharmacol 61(5):775–784PubMedCrossRef
67.
Marano CW, Laughlin KV, Russo LM, Peralta Soler A, Mullin JM (1993) Long-term effects of tumor necrosis factor on LLC-PK1 transepithelial resistance. J Cell Physiol 157(3):519–527PubMedCrossRef
68.
Grant-Tschudy KS, Wira CR (2005) Paracrine mediators of mouse uterine epithelial cell transepithelial resistance in culture. J Reprod Immunol 67(1–2):1–12PubMedCrossRef
69.
Mullin JM, Snock KV (1990) Effect of tumor necrosis factor on epithelial tight junctions and transepithelial permeability. Cancer Res 50(7):2172–2176PubMed
70.
Fish SM, Proujansky R, Reenstra WW (1999) Synergistic effects of interferon gamma and tumour necrosis factor alpha on T84 cell function. Gut 45(2):191–198PubMedCrossRef
71.
Wang F, Graham WV, Wang Y, Witkowski ED, Schwarz BT, Turner JR (2005) Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression. Am J Pathol 166(2):409–419PubMedCrossRef
72.
Sonis ST (2002) The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med 13(5):380–389PubMedCrossRef
73.
Marcus BC, Wyble CW, Hynes KL, Gewertz BL (1996) Cytokine-induced increases in endothelial permeability occur after adhesion molecule expression. Surgery 120(2):411–416 discussion 416–417PubMedCrossRef
74.
Desai TR, Leeper NJ, Hynes KL, Gewertz BL (2002) Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway. J Surg Res 104(2):118–123PubMedCrossRef
75.
Berkes J, Viswanathan VK, Savkovic SD, Hecht G (2003) Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation. Gut 52(3):439–451PubMedCrossRef
76.
Wu Z, Milton D, Nybom P, Sjo A, Magnusson KE (1996) Vibrio cholerae hemagglutinin/protease (HA/protease) causes morphological changes in cultured epithelial cells and perturbs their paracellular barrier function. Microb Pathog 21(2):111–123PubMedCrossRef
77.
Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh AS, Burns J, Keefe DM (2007) Chemotherapy-induced diarrhea is associated with changes in the luminal environment in the DA rat. Exp Biol Med 232(1):96–106
78.
Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh AS, Keefe DM (2008) Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats. Cancer Biol Ther 7(12):1919–1925PubMedCrossRef
79.
Knutton S, Lloyd DR, McNeish AS (1987) Adhesion of enteropathogenic Escherichia coli to human intestinal enterocytes and cultured human intestinal mucosa. Infect Immun 55(1):69–77PubMed
80.
Muza-Moons MM, Schneeberger EE, Hecht GA (2004) Enteropathogenic Escherichia coli infection leads to appearance of aberrant tight junctions strands in the lateral membrane of intestinal epithelial cells. Cell Microbiol 6(8):783–793PubMedCrossRef
81.
Singh U, Van Itallie CM, Mitic LL, Anderson JM, McClane BA (2000) CaCo-2 cells treated with Clostridium perfringens enterotoxin form multiple large complex species, one of which contains the tight junction protein occludin. J Biol Chem 275(24):18407–18417PubMedCrossRef
82.
Sonoda N, Furuse M, Sasaki H, Yonemura S, Katahira J, Horiguchi Y, Tsukita S (1999) Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: evidence for direct involvement of claudins in tight junction barrier. J Cell Biol 147(1):195–204PubMedCrossRef
83.
Bjarnason I, MacPherson A, Hollander D (1995) Intestinal permeability: an overview. Gastroenterology 108(5):1566–1581PubMedCrossRef
84.
Keefe DM, Brealey J, Goland GJ, Cummins AG (2000) Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans. Gut 47(5):632–637PubMedCrossRef
85.
Hamada K, Shitara Y, Sekine S, Horie T (2010) Zonula Occludens-1 alterations and enhanced intestinal permeability in methotrexate-treated rats. Cancer Chemother Pharmacol 66(6):1031–1038PubMedCrossRef
86.
Maeda T, Miyazono Y, Ito K, Hamada K, Sekine S, Horie T (2010) Oxidative stress and enhanced paracellular permeability in the small intestine of methotrexate-treated rats. Cancer Chemother Pharmacol 65(6):1117–1123PubMedCrossRef
87.
Chen Y, Lu Q, Schneeberger EE, Goodenough DA (2000) Restoration of tight junction structure and barrier function by down-regulation of the mitogen-activated protein kinase pathway in ras-transformed Madin-Darby canine kidney cells. Mol Biol Cell 11(3):849–862PubMed
88.
Basuroy S, Seth A, Elias B, Naren AP, Rao R (2006) MAPK interacts with occludin and mediates EGF-induced prevention of tight junction disruption by hydrogen peroxide. Biochem J 393(Pt 1):69–77PubMed
89.
Youmba SB, Belmonte L, Galas L, Boukhettala N, Bole-Feysot C, Dechelotte P, Coeffier M (2011) Methotrexate Modulates Tight Junctions Through NF-kappaB, MEK and JNK Pathways. J Pediatr Gastroenterol Nutr 54(4):463–470CrossRef
Metadata
Title
Chemotherapy-induced gut toxicity: are alterations to intestinal tight junctions pivotal?
Authors
Hannah R. Wardill
Joanne M. Bowen
Rachel J. Gibson
Publication date
01-11-2012
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2012
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-012-1989-5

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