CAR and Integrin Expression in Tumors

Examinations of CAR levels in neoplastic cells, revealed that CAR expression is typically low in tumors, including gliomas (18). Indeed, in a study from our group, nearly 50% of glioma cell lines expressed very low levels of CAR (18). Likewise, studies of paraffin-fixed brain tumor surgical specimens have documented the low CAR expression in gliomas in situ. This finding is important because a low-CAR level on tumor cells reduces viral infection and attenuates lateral spread of replication-competent viruses resulting from dependence on CAR for efficient viral infectivity. In addition, low-CAR expression on tumor cells can theoretically result in sequestration of virus by high-CAR expressing noncancerous normal cells, thereby limiting the infection of low-CAR expressing cancer cells. However, in contrast with their frequent low levels of CAR expression, tumor cells typically show high levels of or a^P5. Indeed, in our study, glioma cell lines almost universally demonstrated high levels of or a^P5, and many gliomas showed high expression of both integrins (18).

Fig. 9. Comparison between A 24 and A 24-RGD. The RGD motif in the penton base binds to inte-grins. Insertion of an RGD-motif into the fiber knob, permits A 24-RGD to infect cells irrespective of the presence of CAR. Note that A 24-RGD is still able to bind CAR.

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