In immunohistochemical studies significant differences have been detected in claudin 3 expression between squamous cell and adenocarcinomas the latter displaying stronger expression [40, 82, 83] . Some studies also report significant differences in the expression of claudin 1, 4, 5 and 7 between these two tumor groups [81, 82] . In the study of Paschoud et al squamous cells and adenocarcinomas could be discriminated by the expression of claudins 1 and 5 because adenocarcinomas displayed strong positivity for claudin 5 and weak positivity for claudin 1, while the opposite could be detected in squamous cell carcinomas [81] . Chao et al studied claudin 1 expression in adenocarcinoma and found that a low expression of claudin 1 was associated with a worse survival in these tumors both by immunohistochemistry and mRNA expression [84] . Transfection of claudin 1 into CL1-5 lung carcinoma cells changed the cells to less invasive, less metastatic and less mobile, and their morphology changed to a more epithelial one [84] . Such changes could also be reversed by blocking claudin 1 mRNA expression by siRNA. Oligonucleotide microarray analysis showed a twofold change in 773 genes due to claudin 1 overexpression involving different cellular functions associated with signaling cascades, cellular associations, apoptosis and cytoskeletal regulation. They, however, found that claudin 1 overexpressing cells were able to activate MMP2 [84] . Similar results of claudin expression on MMP activities have been detected in other cell lines. In colon carcinoma CaCo-2 cells, invasion induced by claudin 4 overexpression was due to activation of both MMP2 and MMP9 the mRNA expression of which also increased at the same time [85] . Claudin 5 along with claudins 2, 3 and 4 has been shown to activate matrix metalloproteinases [86] . Claudin overexpression in cancer cells may thus be one factor promoting tumor spread.