Human urinary bladder carcinomas express adenovirus attachment and internalization receptors.
The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)beta(3) and/or alpha(v)beta(5) are needed. Since there have been reports of loss of CVADR in bladder cancer cell lines, we wanted to investigate the expression of this receptor in bladder carcinoma biopsies. Surgical biopsies, as well as five human bladder cancer cell lines, were analyzed for expression of CVADR, the integrins alpha(v)beta(3) and alpha(v)beta(5) and MHC class I. Further, we studied the ability to transduce these cell lines using adenoviral vectors. Immunohistochemistry revealed that all biopsies (27/27) were positive for CVADR. Some variation in expression was evident, and superficially growing tumors stained more strongly than invasive ones. Most human tumors expressed the integrin alpha(v)beta(5) (14/24), whereas integrin alpha(v)beta(3) was less frequently seen (3/20). The established cell lines were efficiently transduced with adenoviral vectors, and transduction could be reduced with anti-CVADR antibodies. The abundance of appropriate viral receptors on tumor biopsy cells is a further argument for using adenoviral vectors in gene therapy of bladder cancer.
Loskog
A
A
Clinical Immunology Division, Rudbeck Laboratory, University of Uppsala, Uppsala, Sweden.
Hedlund
T
T
Wester
K
K
de la Torre
M
M
Philipson
L
L
Malmström
P-U
PU
Tötterman
T H
TH
D000256:Adenoviridae / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002277:Carcinoma / Q000737:chemistry*; D004770:Enterovirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D016023:Integrins / Q000032:analysis; D011991:Receptors, Virus / Q000032:analysis* / Q000276:immunology; D019030:Receptors, Vitronectin / Q000032:analysis; D014161:Transduction, Genetic / Q000379:methods; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D016023:Integrins; D011991:Receptors, Virus; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5