The coxsackie- and adenovirus receptor (CAR) is an in vivo marker for epithelial tight junctions, with a potential role in regulating permeability and tissue homeostasis

Raschperger, Elisabeth; Thyberg, Johan; Pettersson, Sven; Philipson, Lennart; Fuxe, Jonas; Pettersson, Ralf F.

doi:10.1016/j.yexcr.2006.01.025

Cited by 138 publications

(149 citation statements)

References 58 publications

(79 reference statements)

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“…5,22,31 In contrast to these reports and this study Heideman et al 4 described high CAR expression in esophageal squamous epithelium employing immunohistochemistry. However, no information on CAR distribution within the esophageal epithelium is given.…”

Section: Discussioncontrasting

confidence: 76%

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Expression and function of the coxsackie and adenovirus receptor in Barrett's esophagus and associated neoplasia

et al. 2009

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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.

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Section: Discussioncontrasting

confidence: 76%

“…This may be of impact because restricted CAR immunopositivity has been seen previously and in this study within the basal layers. 5,31 Furthermore, the use of the antibody RmcB, derived from a mouse hybridoma cell line, may explain the diverging results.…”

Section: Discussionmentioning

confidence: 99%

Expression and function of the coxsackie and adenovirus receptor in Barrett's esophagus and associated neoplasia

et al. 2009

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“…18,26 Consistent with this finding, double immu-nofluorescence labeling experiments revealed a punctate co-localization of CAR with occludin and ZO-1 in the apical and basolateral contacts between the uroepithelial cells in the neonatal and adult bladders. Similarly, CAR was co-localized with occludin and ZO-1 in the mouse choroid plexus, collecting tubule epithelia, and hepatocytes, 11 suggesting that CAR interacts with occludin and ZO-1 at the TJs and adhesion between uroepithelial cells. 27 Thus, the expression of CAR in the underlying, as well as superficial, cells might be integrated as a part of the strategy for virus-mediated gene therapy in the bladder uroepithelium.…”

Section: Commentmentioning

confidence: 94%

“…The lack of an intracellular tail will result in the loss of targeting of CAR to the TJs, and differences in the tail ends between the 2 CAR isoforms (amino acid 340-365 in CAR-1; amino acid 340-352 in CAR-2) affects their subcellular localization. 10,11 Taking into account that CAR-2 mRNA was dominant in the mucosa of the adult bladders, CAR-2 might be recruited to the basolateral contacts, as well as the apical TJs, in the bladder uroepithelium. Currently, however, the differential subcellular localization of CAR isoforms in the bladder uroepithelium remains to be determined.…”

Section: Commentmentioning

confidence: 99%

“…CAR in the epithelial lining plays a role in the regulation of epithelial permeability. 10,11 In addition, CAR promotes conformational changes in the virus capsid that is essential for virus entry and release of viral RNA, 12 suggesting that CAR might influence viral susceptibility or virus-mediated gene delivery in the bladder uroepithelium. Furthermore, CAR interacts with actin and microtubules, leading to dynamic reorganization of the cytoskeleton.…”

mentioning

confidence: 99%

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Expression of Coxsackievirus and Adenovirus Receptor Isoforms in Developing Mouse Bladder Uroepithelium

Gye

Lee

et al. 2011

Urology

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The coxsackievirus and adenovirus receptor: virological and biological beauty

Excoffon

2020

FEBS Letters

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The coxsackievirus and adenovirus receptor (CAR) is an essential multifunctional cellular protein that is only beginning to be understood. CAR serves as a receptor for many adenoviruses, human group B coxsackieviruses, swine vesicular disease virus, and possibly other viruses. While named for its function as a viral receptor, CAR is also involved in cell adhesion, immune cell activation, synaptic transmission, and signaling. Knockout mouse models were first to identify some of these biological functions; however, tissue‐specific model systems have shed light on the complexity of different CAR isoforms and their specific activities. Many of these functions are mediated by the large number of interacting proteins described so far, and several new putative interactions have recently been discovered. As antiviral and gene therapy strategies that target CAR continue to emerge, future work poised to understand the biological implications of manipulating CAR in vivo is critical.

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The coxsackie- and adenovirus receptor (CAR) is an in vivo marker for epithelial tight junctions, with a potential role in regulating permeability and tissue homeostasis

Cited by 138 publications

References 58 publications

Expression and function of the coxsackie and adenovirus receptor in Barrett's esophagus and associated neoplasia

Expression and function of the coxsackie and adenovirus receptor in Barrett's esophagus and associated neoplasia

Expression of Coxsackievirus and Adenovirus Receptor Isoforms in Developing Mouse Bladder Uroepithelium

The coxsackievirus and adenovirus receptor: virological and biological beauty

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