Adenoviral transduction efficiency of ovarian cancer cells can be limited by loss of integrin beta(3) subunit expression and increased by reconstitution of integrin alpha(V)beta(3)

Recombinant adenoviruses expressing a therapeutic gene are currently used i n clinical studies for treatment of advanced ovarian cancer. We therefore t ested whether the expression level of primary (CAR) and secondary adenoviru s receptors (integrins) was predictive of the efficacy of adenoviral gene t ransfer in ovarian cancer cells. Adenoviral transduction efficiency (ATE) w as determined with an E1-deleted adenovirus type 5 expressing beta -galacto sidase under a CMV promoter (AdGal). ATE was studied in relationship to the expression level of both CAR (coxsackie and adenovirus receptor) and integ rins. A representative sample of 25 permanent human cell lines established from advanced ovarian cancer in our laboratory and the OV-2774 cell line we re tested. Overall, ATE increased with increasing titers of AdGal. At a giv en titer of 50 infectious units per cell, transduction efficiency varied fr om 6 to 94% among the individual cell lines. All cell lines expressed CAR a nd integrin alpha (v)beta (5), but no relation between ATE and expression l evel of CAR or alpha (v)beta (5) integrin was observed. In contrast, cell l ines with poor ATE, despite expressing high levels of CAR, lacked expressio n of integrins alpha (v)beta (3) and alpha (5)beta (1). Reconstitution of a lpha (v)beta (3) integrin by reexpressing the beta (3) subunit significantl y enhanced ATE of ovarian cancer cells. In ovarian cancer, neither integrin s nor CAR alone appear to be potentially useful predictive markers for ATE by serotype 5 adenovirus in clinical gene therapy. A minimum level of CAR n ecessary for binding of adenoviruses was observed in all tested ovarian can cer cell lines. Loss of alpha (v)beta (3) integrin is frequently associated with advanced stages of ovarian cancer and can significantly reduce ATE.