Increased adenoviral transduction efficacy in human laryngeal carcinoma cells resistant to cisplatin is associated with increased expression of integrin α_vβ₃ and coxsackie adenovirus receptor

Abstract

In our study, we investigated molecular mechanisms of increased adenoviral transduction efficacy in cisplatin-resistant human laryngeal carcinoma cells CA3 ST

Increased expression of the coxsackie and adenovirus receptor downregulates αvβ3 and αvβ5 integrin expression and reduces cell adhesion and migration

“…However, this is very difficult to achieve experimentally due to the heterodimeric nature of integrins. Namely, the transfected β3 subunit could compete for available αv in a cell and decrease another αv heterodimer like αvβ5, as we described previously in a model of human laryngeal carcinoma cell line (Ambriović-Ristov et al, 2004).…”

Vincristine-resistant human laryngeal carcinoma cells demonstrate increased Rous sarcoma virus promoter activity

“…Drug resistance is the major cause of unsuccessful chemotherapy, and our previously published data on HEp2-derived cisplatin resistant cell lines indicate that cisplatin resistant cells could be a better target for adenovirus gene therapy than the parental tumor cells because they could be infected more efficiently (Ambriović-Ristov et al 2004). We think that promoter activity is often neglected in analyzing the success of nonviral and viral therapeutic gene transfer for tumor therapy, especially in certain drug-resistant tumors that should, in the near future, be the first treated by gene therapy.…”

“…Drug-resistant human bladder cancer cells were shown to be more sensitive to adenovirus-mediated wild-type p53 gene therapy than drug-sensitive cells, but the mechanism was unclear (Shirakawa et al 2001). Our group has previously shown that the increased Ad5 transduction efficiency in a HEp2-derived cell clone resistant to cisplatin is due to the upregulation of the Ad5 receptors CAR and αvβ3 integrin (Ambriović-Ristov et al 2004).…”

“…We have previously reported increased adenoviral transduction efficiency in HEp2 cells resistant to cisplatin due to the upregulation of the CAR and αvβ3 integrin (Ambriović-Ristov et al 2004). To determine whether a similar phenomenon could be observed in HEp2 cells resistant to vincristine, we measured the expression of CAR in parental HEp2 and vincristine-resistant VK2 cells.…”

“…Several reports have suggested that Ad5 vectors transduce drugresistant tumor cells more efficiently than parental cell lines (Ambriović-Ristov et al 2004;Shirakawa et al 2001). However, the relative contribution of increased virus uptake and increased transcription to enhanced transduction is unknown.…”