Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier

Table 1 Claudin expression in the normal human stomach and changes that occur in gastric cancer

	Location	Detection method	Expression (normal stomach)	Patient outcome	Changes in GC
Cldn 1	Unspecified region	SAGE database and RT-PCR[110]	Present	Not evaluated	Present, no change in GC
	Unspecified region	cDNA oligonucleotide microarray analysis[67]	Present	Up-regulation results in extremely poor outcome	One of the most highly up-regulated genes
	Corpus, antrum	Immunostaining[69]	Strong expression in epithelial cells	No association with patient outcome	Some GC with strong expression and some with no expression
	Antrum	Immunostaining[74]	Strong expression in epithelial cells	No association with patient outcome	No change in expression in GC
	Unspecified region	Immunostaining[68,70]	Not evaluated	Not evaluated	Highly expressed in GC; most highly expressed at invasive front
	Unspecified region	Immunostaining[25]	Tumor margin	Not evaluated	55.4% of cells are positive at the tumor margin
					Reduced expression in GC
	Corpus	Immunostaining[73]	Surface and chief cells ++++; parietal cells +	Not evaluated	Basolateral localization
					Expression in GC is dependent on the expression of RUNX3
Cldn 2	Unspecified region	qRT-PCR[111]	Weak expression	Not evaluated	No change in GC
	Unspecified region	cDNA oligonucleotide microarray analysis[67]	Present	Not evaluated	Highly up-regulated in GC
	Unspecified region	Immunostaining[68,83]	Not evaluated	Not evaluated	Highly expressed in GC
Cldn 3	Unspecified region	SAGE database and RT-PCR[110]	Present	Not evaluated	Up-regulated in GC
	Unspecified region	Immunostaining[112]	Not evaluated	Not evaluated	Higher expression in low grade compared to high-grade malignancy
	Unspecified region	Immunostaining[25,36,68,113-116]	Low to no expression in stomach	Up-regulation has no effect on survival	Highly expressed in the majority of GC’s
				Up-regulation associated with a significantly higher incidence of synchronous and metachronous multiple GC and gastric adenomas[114]	Increase in expression occurs in metaplasia
	Corpus, antrum	Immunostaining[69]	Corpus, strong expression; Antrum, weaker expression	Strong expression results in better outcome.	Some GC with strong expression and some with no expression
	Antrum	Immunostaining[74]	No expression	No association with patient outcome	Most GC weak to moderate expression
Cldn 4	Unspecified region	SAGE database and RT-PCR[17,110]	Present	Not evaluated	Highly up-regulated in GC
	Unspecified region	Immunostaining[112]	Not evaluated	Not evaluated	Higher expression in low grade compared to high-grade malignancy
	Unspecified region	Immunostaining[17,23-26,68,113-117]	Low to no expression in stomach	No association with patient outcome.	Highly expressed in GC
					Localized to the basolateral membrane
					Prominent in intestinal-type GC
	Unspecified region	Immunostaining[126]	Low to no expression in stomach	High expression is associated with favorable prognosis and longer survival; low expression is associated with poor survival	Highly expressed from stages intestinal metaplasia to GC
					Localized to the basolateral membrane
	Corpus, antrum	Immunostaining[69]	Corpus, strong expression; Antrum, weak expression	No association with patient outcome	Strong expression associated with metaplasia
					Some GC with strong expression and some with no expression
	Antrum	Immunostaining[74]	No expression	High expression associated with poor outcome	Intestinal metaplasia highly expressed90% of GC have weak to strong expression
Cldn 5	Unspecified region	SAGE database and RT-PCR[110]	Present	Not evaluated	Present, no change in GC
	Corpus, antrum	Immunostaining[69]	Corpus, strong expression; Antrum weak expression.	No association with patient outcome.	Some GC with strong expression and some with weak expression.
Cldn 7	Unspecified region	SAGE database and RT-PCR[110]	Present	Not evaluated	Highly up-regulated in GC
	Unspecified region	cDNA oligonucleotide microarray analysis[67]	Present	Not evaluated	Highly up-regulated in GC
	Unspecified region	Immunostaining[36]	Not present in stomach	Up-regulation correlated with poor survival	Highly up-regulated in GC
Cldns 8-12	Unspecified region	SAGE database and RT-PCR[110]	Present	Not evaluated	Present, no change in GC
Cldn 10	Unspecified region	Immunostaining[118]	Highly expressed	Not evaluated	Significantly reduced in GC
Cldn 11	Unspecified region	RT-PCR methylation analysis[119]	Not evaluated	Not evaluated	Highly methylated in gastric cancer, which is correlated to attenuated expression.
Cldn 14	Unspecified region	Immunostaining[118]	Little to no expression	Not evaluated	Highly expressed in GC
					Localization to the basolateral membrane
Cldn 16	Unspecified region	SAGE database and RT-PCR	No expression	Not evaluated	No expression in GC
Cldn 17	Unspecified region	Immunostaining[118]	Highly expressed	Not evaluated	Significantly reduced in GC
Cldn 18	Unspecified region	SAGE database and/or RT-PCR[110,34,36]	Not evaluated	Down-regulation correlated with poor survival	Identified as a highly expressed gene that is significantly down-regulated in GC
	Unspecified region	RT-PCR[34,120]	Not evaluated	Not evaluated	Cldn18A1 is not expressed in stomach or in GC whereas Cldn18A2 is expressed in stomach and in some GC’s
	Corpus or antrum	Immunostaining[34,37,113]	Surface, ++++Pit, +Parietal/Neck, +++Zymogenic, +++	Down-regulation correlated with poor survival	Basolateral localization.
					Attenuation is an early event, which occurs in the metaplastic mucosa
Cldns 21, 22, 23, 24	Database search	Bioinformatics[121]	Not evaluated	Not evaluated	Identified genes for Cldns 21-24
Cldn 23	Unspecified region	Genome-wide analysis[122]	Not evaluated	Not evaluated	Cldn-23 down-regulated in 78.9% of GC with an intestinal phenotype

++++, very highly expressed; +, weak expression. Cldn: Claudin; GC: Gastric cancer.

Table 2 Characteristics of human gastric cell lines that are used to study the role of Helicobacter pylori in tight junction dysfunction during infection

Cultured cell line	ZO-1, 2, or 3	Occludin	JAM’s	Tricellulin	Cldns	Confluency	Ref.	Cldns not expressed
AGS	ZO-1				2, 4, 6, 7, 9	Confluent monolayer with no TER	[82,92,123-126]	11[119]
BGC-823			JAM-A (low)		1, 18		[19,38,71]
GES-1			JAM-A (high)				[19]
HFE-145					11		[119]
HGE-20	ZO-1				4	Confluent monolayer with TER-polarized	[65,80,81]
HS-746T					1		[71]
HSC-39					2		[111]	18[34]
HSC-45				Yes			[16]
HSC-57				Yes			[16]
HSC-59				Yes			[16]
KATOIII	ZO-1	Yes			1, 2, 4, 18		[38,71,72,111, 126,127]	11[119], 18[34]
MKN-1								4[126], 18[34]
MKN-7	ZO-1	Yes		Yes	4		[16,127]	18[34]
MKN-28	ZO-1	Yes	JAM-A		1, 3, 4, 7	Confluent monolayer with a TER	[64,71,72,126-128]	11[119], 18[34]
MKN-45	ZO-1	Yes			1, 2, 3, 4, 18	Isolated cell clumps	[34,71,72,108,111,127]
MKN-74				Yes	2, 4, 18		[16,34,37,38,111,126]	18[108]
MUGC4					1		[72]
NCI-N87	ZO-1				1, 4, 18	Confluent monolayer with a moderate TER	[38,66,71,126]
NUGC-3								18[108]
SIIA								11[119]
SCG-7901			JAM-A		1, 18		[19,38,71]
SNU-1								11[119]
SNU-5					4		[126]
SNU-216					4		[126]
SNU-484								4[126]
SNU-601					4		[126]
SNU-620					4		[126]
SNU-638								4[126]
SNU-668								4[126]
SNU-719					4		[126]
TMK-1	ZO-1				1, 3, 4, 7, 12, 15, 18		[129]	18[34]

Cldn: Claudin; ZO: Zonula occludens; TER: Transepithelial (electrical) resistance.