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[Cancer Research 59, 325-330, January 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 325-330, January 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Loss of Adenoviral Receptor Expression in Human Bladder Cancer Cells: A Potential Impact on the Efficacy of Gene Therapy1

Yingming Li2, Rey-Chen Pong2, Jeffrey M. Bergelson, M. Craig Hall, Arthur I. Sagalowsky, Ching-Ping Tseng, Zhi Wang and Jer-Tsong Hsieh3

Department of Urology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas [Y. L., R-C. P., M. C. H., A. I. S., C-P. T., Z. W., J-T. H.], and Division of Immunologic and Infectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania [J. M. B.]

There is great interest in the development of gene therapeutic strategies for the treatment of benign and malignant diseases. Recombinant adenovirus has a wide spectrum of tissue specificity and is an efficient vector delivery system. Successful gene delivery, however, requires viral entry into the target cells via specific receptor-mediated uptake. Recently, a cDNA clone (the coxsackie and adenovirus receptor [CAR]) encoding a 46-kDa protein was identified as the receptor for group C adenovirus (e.g., adenovirus type 2 and 5). Currently, little is known regarding the expression of adenoviral receptor in normal tissue and cancer. In this paper, we have documented a significant difference in viral receptor levels that may be due to transcriptional regulation of the CAR gene in several human bladder cancer cell lines. The differences in viral receptor levels in these cells correlated with their sensitivity to viral infection. Transfection of receptor-negative cell line with CAR cDNA led to increased virus binding and increased susceptibility to adenovirus-mediated gene delivery. Our results demonstrate that the expression of adenoviral receptor is variable among human bladder cancer cells. This variability may have a significant impact on the outcome of adenovirus-based gene therapy.




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