Significant increase of adenovirus infectivity in glioma cell lines by extracellular domain of hCAR

Recombinant adenoviruses are highly advantageous as vectors for transferrin g genes into mammalian cells, but the transfer is not efficient in all type s of cells. We investigated the effects of four adenoviral receptors [integ rin alpha v, integrin beta 3, integrin beta 5, and human coxsackievirus and adenovirus receptor (hCAR)] on adenovirus-mediated transfer of exogenous c DNA into each of 10 glioma cell lines. Transfection efficiency varied widel y from one cell line to another (0-100%) when we measured it by infection w ith AdLacZ, a vector designed to express P-galactosidase. Levels of integri n alpha v and integrin beta 5 expression were similar among the 10 cell lin es, but expression of hCAR and integrin beta 3 varied significantly. As the se observations indicated a possible correlation between expression of hCAR and the efficiency of gene transfer, we induced the hCAR gene into three g lioma cell lines (T98G, U118MG, and U138MG) that expressed hCAR at very low levels and had also revealed low efficiencies of adenoviral gene transfer. In U118MG- and U138MG-derived cells that had regained the ability to expre ss hCAR in stable fashion, adenovirus-mediated gene transfer became highly efficient. Moreover, addition of the peptide corresponding to the extracell ular domain of hCAR (ECD-hCAR) by preincubation significantly increased the adenovirus infectivity to these adenovirus-tolerant cells. These results s uggest that hCAR could be one of important determinants of the infectivity of adenovirus: and that the ECD-hCAR might be a novel useful tool for impro vement of adenovirus-mediated gene therapy against the adenovirus-tolerant cancer cells.