Integrin αv and coxsackie adenovirus receptor expression in clinical bladder cancer

Markus D. Sachs, Katherine A. Rauen, Meera Ramamurthy, Jennifer L. Dodson, Angelo M. De Marzo, Mathew J. Putzi, Mark P. Schoenberg, Ronald Rodriguez

Research output: Contribution to journalArticle

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Abstract

Objectives. To evaluate the expression of the coxsackie and adenovirus receptor (CAR) and αv integrins in clinical specimens of bladder cancer to determine the susceptibility to adenoviral gene therapy. Efficient adenovirus-based gene therapy requires binding of the virus to CAR and involves the αv integrins. Studies on bladder cancer cell lines have shown that low adenoviral transduction rates were associated with low-level expression of CAR. Integrin αv expression increases in various tumors suggest its importance in differentiation, proliferation, and migration. CAR is structurally a member of the Ig-type superfamily of cell-cell adhesion molecules, suggesting that its expression may also be related to the state of tumor differentiation. Methods. We performed immunohistochemistry for CAR and integrin αv expression in bladder cancer specimens in 50 paraffin-embedded tumor-normal pairs and confirmed the results by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of 11 separate bladder tumors and 4 separate normal bladder controls. Results. Immunochemistry demonstrated a stage and grade-dependent decrease in CAR expression (90.0%, 83.3%, and 31.3% of normal urothelium and superficial and invasive transitional cell carcinoma [TCC] and 83.3% and 39.5% of low and high-grade TCC, respectively). Furthermore, we found a stage and grade-dependent increase in αv integrin expression (13.3%, 46.0%, and 56.3% of normal urothelium, superficial TCC, and invasive TCC and 25% and 52.6% of low and high-grade TCC, respectively). Quantitative RT-PCR analysis confirmed a downregulation at the CAR gene expression level. Conclusions. This down-regulation may have a major impact on developing adenoviral-based gene therapy modalities. In addition, we propose that loss of CAR expression decreases rigid cell adhesion, possibly increasing the migratory potential. Loss of CAR expression correlates with the invasive phenotype in our analysis of bladder cancer. Simultaneously, the finding of increased αv expression in invasive cancer suggests a pathogenesis that involves heterophilic adhesion and migration of these cells on various extracellular ligands.

Original languageEnglish (US)
Pages (from-to)531-536
Number of pages6
JournalUrology
Volume60
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

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Coxsackie and Adenovirus Receptor-Like Membrane Protein
Urinary Bladder Neoplasms
Integrins
Transitional Cell Carcinoma
Genetic Therapy
Urothelium
Reverse Transcriptase Polymerase Chain Reaction
Cell Adhesion
Neoplasms
Down-Regulation
Immunochemistry
Virus Attachment
Cell Adhesion Molecules
Adenoviridae
Paraffin
Cell Movement
Urinary Bladder
Immunohistochemistry

ASJC Scopus subject areas

  • Urology

Cite this

Sachs, M. D., Rauen, K. A., Ramamurthy, M., Dodson, J. L., De Marzo, A. M., Putzi, M. J., ... Rodriguez, R. (2002). Integrin αv and coxsackie adenovirus receptor expression in clinical bladder cancer. Urology, 60(3), 531-536. https://doi.org/10.1016/S0090-4295(02)01748-X

Integrin αv and coxsackie adenovirus receptor expression in clinical bladder cancer. / Sachs, Markus D.; Rauen, Katherine A.; Ramamurthy, Meera; Dodson, Jennifer L.; De Marzo, Angelo M.; Putzi, Mathew J.; Schoenberg, Mark P.; Rodriguez, Ronald.

In: Urology, Vol. 60, No. 3, 2002, p. 531-536.

Research output: Contribution to journalArticle

Sachs, MD, Rauen, KA, Ramamurthy, M, Dodson, JL, De Marzo, AM, Putzi, MJ, Schoenberg, MP & Rodriguez, R 2002, 'Integrin αv and coxsackie adenovirus receptor expression in clinical bladder cancer', Urology, vol. 60, no. 3, pp. 531-536. https://doi.org/10.1016/S0090-4295(02)01748-X
Sachs MD, Rauen KA, Ramamurthy M, Dodson JL, De Marzo AM, Putzi MJ et al. Integrin αv and coxsackie adenovirus receptor expression in clinical bladder cancer. Urology. 2002;60(3):531-536. https://doi.org/10.1016/S0090-4295(02)01748-X
Sachs, Markus D. ; Rauen, Katherine A. ; Ramamurthy, Meera ; Dodson, Jennifer L. ; De Marzo, Angelo M. ; Putzi, Mathew J. ; Schoenberg, Mark P. ; Rodriguez, Ronald. / Integrin αv and coxsackie adenovirus receptor expression in clinical bladder cancer. In: Urology. 2002 ; Vol. 60, No. 3. pp. 531-536.
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abstract = "Objectives. To evaluate the expression of the coxsackie and adenovirus receptor (CAR) and αv integrins in clinical specimens of bladder cancer to determine the susceptibility to adenoviral gene therapy. Efficient adenovirus-based gene therapy requires binding of the virus to CAR and involves the αv integrins. Studies on bladder cancer cell lines have shown that low adenoviral transduction rates were associated with low-level expression of CAR. Integrin αv expression increases in various tumors suggest its importance in differentiation, proliferation, and migration. CAR is structurally a member of the Ig-type superfamily of cell-cell adhesion molecules, suggesting that its expression may also be related to the state of tumor differentiation. Methods. We performed immunohistochemistry for CAR and integrin αv expression in bladder cancer specimens in 50 paraffin-embedded tumor-normal pairs and confirmed the results by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of 11 separate bladder tumors and 4 separate normal bladder controls. Results. Immunochemistry demonstrated a stage and grade-dependent decrease in CAR expression (90.0{\%}, 83.3{\%}, and 31.3{\%} of normal urothelium and superficial and invasive transitional cell carcinoma [TCC] and 83.3{\%} and 39.5{\%} of low and high-grade TCC, respectively). Furthermore, we found a stage and grade-dependent increase in αv integrin expression (13.3{\%}, 46.0{\%}, and 56.3{\%} of normal urothelium, superficial TCC, and invasive TCC and 25{\%} and 52.6{\%} of low and high-grade TCC, respectively). Quantitative RT-PCR analysis confirmed a downregulation at the CAR gene expression level. Conclusions. This down-regulation may have a major impact on developing adenoviral-based gene therapy modalities. In addition, we propose that loss of CAR expression decreases rigid cell adhesion, possibly increasing the migratory potential. Loss of CAR expression correlates with the invasive phenotype in our analysis of bladder cancer. Simultaneously, the finding of increased αv expression in invasive cancer suggests a pathogenesis that involves heterophilic adhesion and migration of these cells on various extracellular ligands.",
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AU - Sachs, Markus D.

AU - Rauen, Katherine A.

AU - Ramamurthy, Meera

AU - Dodson, Jennifer L.

AU - De Marzo, Angelo M.

AU - Putzi, Mathew J.

AU - Schoenberg, Mark P.

AU - Rodriguez, Ronald

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AB - Objectives. To evaluate the expression of the coxsackie and adenovirus receptor (CAR) and αv integrins in clinical specimens of bladder cancer to determine the susceptibility to adenoviral gene therapy. Efficient adenovirus-based gene therapy requires binding of the virus to CAR and involves the αv integrins. Studies on bladder cancer cell lines have shown that low adenoviral transduction rates were associated with low-level expression of CAR. Integrin αv expression increases in various tumors suggest its importance in differentiation, proliferation, and migration. CAR is structurally a member of the Ig-type superfamily of cell-cell adhesion molecules, suggesting that its expression may also be related to the state of tumor differentiation. Methods. We performed immunohistochemistry for CAR and integrin αv expression in bladder cancer specimens in 50 paraffin-embedded tumor-normal pairs and confirmed the results by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of 11 separate bladder tumors and 4 separate normal bladder controls. Results. Immunochemistry demonstrated a stage and grade-dependent decrease in CAR expression (90.0%, 83.3%, and 31.3% of normal urothelium and superficial and invasive transitional cell carcinoma [TCC] and 83.3% and 39.5% of low and high-grade TCC, respectively). Furthermore, we found a stage and grade-dependent increase in αv integrin expression (13.3%, 46.0%, and 56.3% of normal urothelium, superficial TCC, and invasive TCC and 25% and 52.6% of low and high-grade TCC, respectively). Quantitative RT-PCR analysis confirmed a downregulation at the CAR gene expression level. Conclusions. This down-regulation may have a major impact on developing adenoviral-based gene therapy modalities. In addition, we propose that loss of CAR expression decreases rigid cell adhesion, possibly increasing the migratory potential. Loss of CAR expression correlates with the invasive phenotype in our analysis of bladder cancer. Simultaneously, the finding of increased αv expression in invasive cancer suggests a pathogenesis that involves heterophilic adhesion and migration of these cells on various extracellular ligands.

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