Coxsackievirus–adenovirus receptor expression in ovarian cancer cell lines is associated with increased adenovirus transduction efficiency and transgene expression

Abstract

The expression of coxsackievirus–adenovirus receptor (CAR) and the integrinsαvβ3 and αvβ5 was analyzed quantitatively (flow cytometry) and qualitatively (immunocytochemistry) in five human ovarian cancer cell lines (PEO1, PEO4, PEO14, SKOV-3, and OVCAR-3) and three control cell lines (293, HeLa, and CHO-K1). The transduction efficiencies were evaluated by adv/rsv-β-Gal transduction followed by X-gal staining. The effects of 17β-estradiol on cell growth, CAR and integrins αvβ3/5 expression, adenovirus transduction efficiency, and cell-killing efficacy of adv/rsv-tk plus ganciclovir were determined. The levels of CAR, integrin αvβ3, and integrin αvβ5 showed great variation between the cell lines. Whereas the expression of CAR appeared to be essential for and positively correlated with adenovirus transduction efficiency, the integrins αvβ3 and αvβ5 were not absolutely necessary for adenovirus transduction even though their presence may facilitate transduction. In PEO4 and PEO1 cells, proliferation was stimulated by 17β-estradiol in a dose-dependent manner. In PEO4 cells, and much less pronounced in PEO1 cells, this was accompanied by an increase in CAR expression. The stimulation of CAR expression was paralleled by an increased transduction efficiency resulting in an increased cell-killing efficacy. Our data suggest that the expression of CAR is one of the most important prerequisites for successful adenovirus-mediated gene therapy of ovarian cancer. Cancer Gene Therapy (2001) 8, 168–175