Gastric carcinoma arises from aberrant growth of normal gastric mucosa. There is increasing evidence that claudins (CLDNs) may play a critical role in the significant steps of gastric tumorigenesis, from metaplasia to metastasis. The CLDN family which consists of at least 27 member proteins is known to mediate selective permeability in cellular tight junctions. It is now established that CLDNs are differentially altered in gastric cancer and CLDN proteins are believed to play different roles in the growth and progression of gastric cancer.
TsukitaS, FuruseM. The structure and function of claudins, cell adhesion molecules at tight junctions. Ann N Y Acad Sci2000;915:129–35
2.
KrauseG, WinklerL, MuellerSL, HaseloffRF, PiontekJ, BlasigIE. Structure and function of claudins. Biochim Biophys Acta2008;1778:631–45
3.
RossMH, PawlinaW. Histology. A Text and Atlas. 6th edn. Baltimore, MD: SAGE Publications, 2011
4.
MinetaK, YamamotoY, YamazakiY, TanakaH, TadaY, SaitoK, TamuraA, IgarashiM, EndoT, TakeuchiK, TsukitaS. Predicted expansion of the claudin multigene family. FEBS Lett2011;585:606–12
5.
AngelowS, AhlstromR, YuASL. Biology of claudins. Am J Physiol Renal Physiol2008;295:F867–76
6.
TamuraA, YamazakiY, HayashiD, SuzukiK, SentaniK, YasuiW, TsukitaS. Claudin-based paracellular proton barrier in the stomach. Ann N Y Acad Sci2012;1258:108–14
7.
HayashiD, TamuraA, TanakaH, YamazakiY, WatanabeS, SuzukiK, SuzukiK, SentaniK, YasuiW, RakugiH, IsakaY, TsukitaS. Deficiency of claudin-18 causes paracellular H+ leakage, up-regulation of interleukin-1β, and atrophic gastritis in mice. Gastroenterology2012;142:292–304
8.
SolerAP, MillerRD, LaughlinKV, CarpNZ, KlurfeldDM, MullinJM. Increased tight junctional permeability is associated with the development of colon cancer. Carcinogenesis1999;20:1425–31
9.
HewittKJ, AgarwalR, MorinPJ. The claudin gene family: expression in normal and neoplastic tissues. BMC Cancer2006;6:186
10.
OubanA, AhmedAA. Claudins in human cancer: a review. Histol Histopathol2010;25:83–90
11.
TurksenK. Claudins and cancer stem cells. Stem Cell Rev2011;7:797–8
12.
MorinPJ. Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res2005;65:9603–6
13.
MullinJM, LaughlinKV, GinanniN, MaranoCW, ClarkeHM, Peralta SolerA. Increased tight junction permeability can result from protein kinase C activation/translocation and act as a tumor promotional event in epithelial cancers. Ann N Y Acad Sci2000;915:231–6
14.
MiyoshiJ, TakaiY. Molecular perspective on tight-junction assembly and epithelial polarity. Adv Drug Deliv Rev2005;57:815–55
15.
FedwickJP, LapointeTK, MeddingsJB, ShermanPM, BuretAG. Helicobacter pylori activates myosin light-chain kinase to disrupt claudin-4 and claudin-5 and increase epithelial permeability. Infect Immun2005;73:7844–52
16.
ShinK, FoggVC, MargolisB. Tight junctions and cell polarity. Annu Rev Cell Dev Biol2006;22:207–35
17.
HollandeF, BlancEM, BaliJP, WhiteheadRH, PelegrinA, BaldwinGS, ChoquetA. HGF regulates tight junctions in new nontumorigenic gastric epithelial cell line. Am J Physiol Gastrointest Liver Physiol2001;280:G910–21
18.
FerlayJ, ShinHR, BrayF, FormanD, MathersC, ParkinDM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer2010;127:2893–917
19.
JemalA, CenterMM, DeSantisC, WardEM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev2010;19:1893–907
20.
SonsHU, BorchardF. Cancer of the distal esophagus and cardia. Incidence, tumorous infiltration, and metastatic spread. Ann Surg1986;203:188–95
21.
LaykeJC, LopezPP. Gastric cancer: diagnosis and treatment options. Am Fam Physician2004;69:1133–40
22.
MatsudaY, SembaS, UedaJ, FukuT, HasuoT, ChibaH, SawadaN, KurodaY, YokozakiH. Gastric and intestinal claudin expression at the invasive front of gastric carcinoma. Cancer Sci2007;98:1014–9
23.
SoiniY, TommolaS, HelinH, MartikainenP. Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype. Virchows Arch2006;448:52–8
24.
OkugawaT, OshimaT, ChenX, HoriK, TomitaT, FukuiH, WatariJ, MatsumotoT, MiwaH. Down-regulation of claudin-3 is associated with proliferative potential in early gastric cancers. Dig Dis Sci2012;57:1562–7
25.
OhtaniS, TerashimaM, SatohJ, SoetaN, SazeZ, KashimuraS, OhsukaF, HoshinoY, KogureM, GotohM. Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival. Gastric Cancer2009;12:43–51
26.
SembaS, HasuoT, SatakeS, NakayamaF, YokozakiH. Prognostic significance of intestinal claudins in high-risk synchronous and metachronous multiple gastric epithelial neoplasias after initial endoscopic submucosal dissection. Pathol Int2008;58:371–7
27.
JungH, JunKH, JungJH, ChinHM, ParkWB. The expression of claudin-1, claudin-2, claudin-3, and claudin-4 in gastric cancer tissue. J Surg Res. 2011;167:e185–91
28.
LaurenP. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at histo-clinical classification. Acta Pathol Microbiol Scand1965;64:31–49
29.
MarrelliD, RovielloF, de ManzoniG, MorgagniP, Di LeoA, SaragoniL, De StefanoA, FolliS, CordianoC, PintoE, Italian Research Group for Gastric Cancer. Different patterns of recurrence in gastric cancer depending on Lauren's histological type: longitudinal study. World J Surg2002;26:1160–5
30.
KamataI, IshikawaY, Akishima-FukasawaY, ItoK, AkasakaY, UzukiM, FujimotoA, MoritaH, TamaiS, MaeharaT, OgataK, ShimokawaR, IgarashiY, MikiK, IshiiT. Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer. J Gastroenterol Hepatol2009;24:1527–33
31.
Rendón-HuertaE, TeresaF, TeresaGM, XochitlGS, GeorginaAF, VeronicaZZ, MontañoLF. Distribution and expression pattern of claudins 6, 7, and 9 in diffuse- and intestinal-type gastric adenocarcinomas. J Gastrointest Cancer2010;41:52–9
32.
LeeSK, MoonJ, ParkSW, SongSY, ChungJB, KangJK. Loss of the tight junction protein claudin 4 correlates with histological growth-pattern and differentiation in advanced gastric adenocarcinoma. Oncol Rep2005;13:193–9
33.
KuoWL, LeeLY, WuCM, WangCC, YuJS, LiangY, LoCH, HuangKH, HwangTL. Differential expression of claudin-4 between intestinal and diffuse-type gastric cancer. Oncol Rep2006;16:729–34
34.
WuCM, LeeYS, WangTH, LeeLY, KongWH, ChenES, WeiML, LiangY, HwangTL. Identification of differential gene expression between intestinal and diffuse gastric cancer using cDNA microarray. Oncol Rep2006;15:57–64
35.
UmeharaY, KimuraT, YoshidaM, ObaN, HaradaY. Metastatic mode of gastric carcinoma by flow cytometric and clinicopathologic parameters. Clin Exp Metastasis1992;10:19–24
36.
KwonMJ, KimSH, JeongHM, JungHS, KimSS, LeeJE, GyeMC, ErkinOC, KohSS, ChoiYL, ParkCK, ShinYK. Claudin-4 overexpression is associated with epigenetic derepression in gastric carcinoma. Lab Invest2011;91:1652–67
37.
JohnsonAH, FriersonHF, ZaikaA, PowellSM, RocheJ, CroweS, MoskalukCA, El-RifaiW. Expression of tight-junction protein claudin-7 is an early event in gastric tumorigenesis. Am J Pathol2005;167:577–84
38.
LeeLY, WuCM, WangCC, YuJS, LiangY, HuangKH, LoCH, HwangTL. Expression of matrix metalloproteinases MMP-2 and MMP-9 in gastric cancer and their relation to claudin-4 expression. Histol Histopathol2008;23:515–21
39.
MurrayGI, DuncanME, ArbuckleE, MelvinWT, FothergillJE. Matrix metalloproteinases and their inhibitors in gastric cancer. Gut1998;43:791–7
40.
MrenaJ, WikstenJP, NordlingS, KokkolaA, RistimäkiA, HaglundC. MMP-2 but not MMP-9 associated with COX-2 and survival in gastric cancer. J Clin Pathol2006;59:618–23
41.
SatakeS, SembaS, MatsudaY, UsamiY, ChibaH, SawadaN, KasugaM, YokozakiH. Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma. Pathol Int2008;58:156–63
42.
LongH, CreanCD, LeeWH, CummingsOW, GabigTG. Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium. Cancer Res2001;61:7878–81
43.
SaekiR, KondohM, KakutaniH, TsunodaSI, MochizukiY, HamakuboT, TsutsumiY, HoriguchiY, YagiK. A novel tumor-targeted therapy using a claudin-4-targeting molecule. Mol Pharmacol2009;76:918–26
44.
ResnickMB, GavilanezM, NewtonE, KonkinT, BhattacharyaB, BrittDE, SaboE, MossSF. Claudin expression in gastric adenocarcinomas: a tissue microarray study with prognostic correlation. Hum Pathol2005;36:886–92
45.
BoireauS, BuchertM, SamuelMS, PannequinJ, RyanJL, ChoquetA, ChapuisH, RebillardX, AvancèsC, ErnstM, JoubertD, MottetN, HollandeF. DNA-methylation-dependent alterations of claudin-4 expression in human bladder carcinoma. Carcinogenesis2007;28:246–58
46.
SanadaY, OueN, MitaniY, YoshidaK, NakayamaH, YasuiW. Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype. J Pathol2006;208:633–42
47.
MatsudaM, SentaniK, NoguchiT, HinoiT, OkajimaM, MatsusakiK, SakamotoN, AnamiK, NaitoY, OueN, YasuiW. Immunohistochemical analysis of colorectal cancer with gastric phenotype: claudin-18 is associated with poor prognosis. Pathol Int2010;60:673–80
48.
KrugSM, GünzelD, ConradMP, LeeIFM, AmashehS, FrommM, YuASL. Charge-selective claudin channels. Ann N Y Acad Sci2012;1257:20–8
49.
WuYL, ZhangS, WangGR, ChenYP. Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion. World J Gastroenterol2008;14:4943–8
50.
ChangTL, ItoK, KoTK, LiuQ, Salto-TellezM, YeohKG, FukamachiH, ItoY. Claudin-1 has tumor suppressive activity and is a direct target of RUNX3 in gastric epithelial cells. Gastroenterology2010;138:255–65.e1
51.
MrsnyRJ, BrownGT, Gerner-SmidtK, BuretAG, MeddingsJB, QuanC, KovalM, NusratA. A key claudin extracellular loop domain is critical for epithelial barrier integrity. Am J Pathol2008;172:905–15
52.
SakamotoH, MutohH, SuganoK. Expression of Claudin-2 in intestinal metaplastic mucosa of Cdx2-transgenic mouse stomach. Scand J Gastroenterol2010;45:1273–80
53.
SongX, LiX, TangY, ChenH, WongB, WangJ, ChenM. Expression of claudin-2 in the multistage process of gastric carcinogenesis. Histol Histopathol2008;23:673–82
54.
AungPP, MitaniY, SanadaY, NakayamaH, MatsusakiK, YasuiW. Differential expression of claudin-2 in normal human tissues and gastrointestinal carcinomas. Virchows Arch2006;448:428–34
55.
CunninghamSC, KamangarF, KimMP, HammoudS, HaqueR, Iacobuzio-DonahueCA, MaitraA, AshfaqR, HustinxS, HeitmillerRE, ChotiMA, LillemoeKD, CameronJL, YeoCJ, SchulickRD, MontgomeryE. Claudin-4, mitogen-activated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions. Cancer Epidemiol Biomarkers Prev2006;15:281–7
56.
MimaS, TsutsumiS, UshijimaH, TakedaM, FukudaI, YokomizoK, SuzukiK, SanoK, NakanishiT, TomisatoW, TsuchiyaT, MizushimaT. Induction of claudin-4 by nonsteroidal anti-inflammatory drugs and its contribution to their chemopreventive effect. Cancer Res2005;65:1868–76
57.
Zavala-ZendejasVE, Torres-MartinezAC, Salas-MoralesB, FortoulTI, MontañoLF, Rendon-HuertaEP. Claudin-6, 7, or 9 overexpression in the human gastric adenocarcinoma cell line AGS increases its invasiveness, migration, and proliferation rate. Cancer Invest2011;29:1–1
58.
OshimaT, MiwaH, JohT. Aspirin induces gastric epithelial barrier dysfunction by activating p38 MAPK via claudin-7. Am J Physiol Cell Physiol2008;295:C800–6
AgarwalR, MoriY, ChengY, JinZ, OlaruAV, HamiltonJP, DavidS, SelaruFM, YangJ, AbrahamJM, MontgomeryE, MorinPJ, MeltzerSJ. Silencing of claudin-11 is associated with increased invasiveness of gastric cancer cells. PloS one2009;4:e8002
61.
SahinU, KoslowskiM, DhaeneK, UsenerD, BrandenburgG, SeitzG, HuberC, TüreciO. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res2008;14:7624–34
62.
YanoK, ImaedaT, NiimiT. Transcriptional activation of the human claudin-18 gene promoter through two AP-1 motifs in PMA-stimulated MKN45 gastric cancer cells. Am J Physiol Gastrointest Liver Physiol2008;294:G336–43
63.
SentaniK, OueN, TashiroT, SakamotoN, NishisakaT, FukuharaT, TaniyamaK, MatsuuraH, ArihiroK, OchiaiA, YasuiW. Immunohistochemical staining of Reg IV and claudin-18 is useful in the diagnosis of gastrointestinal signet ring cell carcinoma. Am J Surg Pathol2008;32:1182–9
64.
KatohM, KatohM. CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family. Int J Mol Med2003;11:683–9