Cell surface presence of the coxsackie and
adenovirus receptor (CAR) is considered a crucial prerequisite for the uptake of attenuated adenovirus. In
cancers, however, a frequent loss of CAR has been noted potentially hampering the success of adenovirus-based
therapy. In esophageal Barrett's
carcinomas and its precursor lesions CAR presence has not been systematically determined yet. Immunohistochemical assessment in tissue specimens of 111 patients revealed CAR-positivity in all cases of
Barrett's esophagus, including various degrees of intraepithelial
neoplasia. In contrast, no considerable CAR presence was seen in squamous esophageal epithelium. Among Barrett's
carcinomas, 93% displayed CAR presence, whereas CAR-negativity was observed preferentially in advanced
cancers. Aiming to evaluate whether this loss of CAR impacts
tumor-
biologic properties of esophageal
adenocarcinomas we studied cell lines OE19 and OE33 and observed an increased proliferation, migration and invasion upon
siRNA-mediated functional CAR knock down. In conclusion, our results indicate that CAR may provide a valuable target for adenovirus-based
therapy of Barrett's
carcinomas and its precursor lesions. These data do also suggest that CAR does not contribute substantially to
carcinogenesis in
Barrett's esophagus, however, it may be speculated that loss of CAR promotes
tumor progression in advanced stages of Barrett's
carcinomas.