DOI: 10.1073/pnas.0337599100. Disruption of 3D tissue integrity facilitates adenovirus infection by deregulating the coxsackievirus and adenovirus receptor

Disruption of 3D tissue integrity facilitates adenovirus infection by deregulating the coxsackievirus and adenovirus receptor

10.1073/pnas.0337599100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The human coxsackievirus and adenovirus receptor (CAR) represents the primary cellular site of adenovirus attachment during infection. An understanding of the mechanisms regulating its expression could contribute to improving efficacy and safety of adenovirus-based therapies. We characterized regulation of CAR expression in a 3D cell culture model of human breast cancer progression, which mimics aspects of the physiological tissue context in vitro. Phenotypically normal breast epithelial cells (S1) and their malignant derivative (T4-2 cells) were grown either on tissue culture plastic (2D) or 3D cultures in basement membrane matrix. S1 cells grown in 3D showed low levels of CAR, which was expressed mainly at cell–cell junctions. In contrast, T4-2 cells expressed high levels of CAR, which was mainly in the cytoplasm. When signaling through the epidermal growth factor receptor was inhibited in T4-2 cells, cells reverted to a normal phenotype, CAR protein expression was significantly reduced, and the protein relocalized to cell–cell junctions. Growth of S1 cells as 2D cultures or in 3D in collagen-I, a nonphysiological microenvironment for these cells, led to up-regulation of CAR to levels similar to those in T4-2 cells, independently of cellular growth rates. Thus, expression of CAR depends on the integrity and polarity of the 3D organization of epithelial cells. Disruption of this organization by changes in the microenvironment, including malignant transformation, leads to up-regulation of CAR, thus enhancing the cell's susceptibility to adenovirus infection.

Bibliography

Anders, M., Hansen, R., Ding, R.-X., Rauen, K. A., Bissell, M. J., & Korn, W. M. (2003). Disruption of 3D tissue integrity facilitates adenovirus infection by deregulating the coxsackievirus and adenovirus receptor. Proceedings of the National Academy of Sciences, 100(4), 1943â1948.

Authors 6

M. Anders (first)
R. Hansen (additional)
R.-X. Ding (additional)
K. A. Rauen (additional)
M. J. Bissell (additional)
W. Michael Korn (additional)

References 31 Referenced 90

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Dates

Type	When
Created	22 years, 6 months ago (Feb. 18, 2003, 3:04 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 8:58 a.m.)
Indexed	1 month, 1 week ago (July 24, 2025, 7:53 a.m.)
Issued	22 years, 6 months ago (Feb. 7, 2003)
Published	22 years, 6 months ago (Feb. 7, 2003)
Published Online	22 years, 6 months ago (Feb. 7, 2003)
Published Print	22 years, 6 months ago (Feb. 18, 2003)

Funders 0

None

BibTeX

@article{Anders_2003, title={Disruption of 3D tissue integrity facilitates adenovirus infection by deregulating the coxsackievirus and adenovirus receptor}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0337599100}, DOI={10.1073/pnas.0337599100}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Anders, M. and Hansen, R. and Ding, R.-X. and Rauen, K. A. and Bissell, M. J. and Korn, W. Michael}, year={2003}, month=feb, pages={1943–1948} }

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