Human urinary bladder carcinomas express adenovirus attachment and internalization receptors

Area of Science:

• Oncology
• Virology
• Gene Therapy

Background:

• Adenoviral vectors are potent gene delivery systems.
• Effective gene delivery requires Coxsackievirus/adenovirus receptor (CVADR) and integrins on target cells.
• Previous reports indicated potential loss of CVADR in bladder cancer cell lines.

Purpose of the Study:

• To investigate the expression of CVADR and specific integrins in bladder carcinoma biopsies.
• To assess the suitability of adenoviral vectors for gene therapy in bladder cancer.

Main Methods:

• Immunohistochemistry was used to analyze surgical biopsies and bladder cancer cell lines for CVADR, integrins alpha(v)beta(3) and alpha(v)beta(5), and MHC class I expression.
• Transduction efficiency of adenoviral vectors in cell lines was evaluated.
• The effect of anti-CVADR antibodies on transduction was studied.

Main Results:

• All analyzed bladder cancer biopsies (27/27) expressed CVADR, with higher expression in superficial tumors compared to invasive ones.
• Integrin alpha(v)beta(5) was expressed in most tumors (14/24), while alpha(v)beta(3) was less common (3/20).
• Established bladder cancer cell lines demonstrated efficient transduction with adenoviral vectors, which was inhibitable by anti-CVADR antibodies.

Conclusions:

• The consistent expression of CVADR in bladder cancer biopsies supports the use of adenoviral vectors for gene therapy.
• The presence of necessary viral receptors on tumor cells is a key factor for successful adenoviral vector-mediated gene delivery in bladder cancer.