Naslov
Increased Ad5-mediated transgene expression in cisplatin-resistant human laryngeal carcinoma cells

Autori
Vukić, Dunja ; Majhen, Dragomira ; Stojanović, Nikolina ; Brozović, Anamaria ; Osmak, Maja ; Ambriović-Ristov, Andreja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
Book od Abstract HDIR-1 From Bench to Clinic / Sabol, M. and Levanat, S - Zagreb : Hrvatsko društvo za istraživanje raka (HDIR), 2010, 38-38

Skup
HDIR-1 From Bench to Clinic First meeting with international participation

Mjesto i datum
Zagreb, Hrvatska, 11.11.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Ad5-mediated transgene expression; cisplatin resistance

Sažetak
Adenovirus type 5 (Ad5) based vectors are most common vectors for cancer gene therapy. Coxsackie adenovirus receptor (CAR) has been identified as receptor for Ad5 attachment. Multiple types of integrin molecules that include αvβ3, αvβ5, αvβ1, α5β1 and α3β1 have been shown to act as secondary receptors for Ad5. Several reports have suggested that Ad5 vectors transduce drug-resistant cancer cells more efficiently and/or that drug-resistant cells show increased Ad5-mediated transgene expression compared to parental cell lines. Therefore, Ad5 gene therapy may be a useful approach for the treatment of cancers that were previously subjected to chemotherapy, as drug-resistant tumors may be a better target for Ad5 gene therapy than primary tumors. The present study indicates that cisplatin-resistant human laryngeal carcinoma CK2 cells show increased Ad5-mediated transgene expression compared to parental HEp2 cell line. Using flow cytometry, altered expression of CAR, integrins αvβ5 and α3β1 and integrin subunits αv, β1 and α5 was recorded. We found downregulation of integrin heterodimer αvβ5 as well as αv integrin subunit and upregulation of CAR, integrin heterodimer α3β1 as well as α5 and β1 integrin subunits. Semiquantitative PCR revealed increased attachment and equal internalization of Ad5RSVβgal in CK2 cells as compared to HEp2 cells. Using several recombinant retargeted Ad5, it was shown that none of the surface molecules which expression is altered in CK2 cells is crucial for the increased Ad5-mediated transgene expression. Based on aforementioned data, it can be hypothesized that the cause of increased Ad5-mediated transgene expression is in different intracellular trafficking of Ad5 in CK2 cells as compared to parental HEp2 cells. In addition, the role of α3β1 integrin, that showed the highest extent of upregulation in CK2 cells compared to HEp2 cells, in cisplatin resistance was examined using siRNA-mediated silencing of α3 integrin subunit. It was shown that observed upregulation of integrin α3β1 in CK2 cells is not the cause of cisplatin resistance. Our results confirm that drug-resistant cells could be better targets for Ad5-mediated gene therapy than the initial tumors. Since obtaining in vivo data concerning drug-resistant cells is quite difficult, in vitro investigation may enable us to understand the general mechanisms that could be exploited in tumor gene therapy.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA