Naslov
Changes in cell adhesion proteins induced by the treatment with cisplatin and their role in cisplatin-resistance

Autori
Osmak, Maja ; Brozović, Anamaria ; Čimbora Zovko, Tamara ; Majhen, Dragomira ; Fritz, Gerhard ; Ambriović Ristov, Andreja

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

Izvornik
Abstracts of the 13th World Congress on Advances in Oncology, and 11th International Symposium on Molecular Medicine ; u: International Journal of Molecular Medicine. Supplement / Spandidos, D.A. - Atena : Lychnia, Greece, 2008, S61-S61

Skup
The 13th World Congress on Advances in Oncology, and 11th International Symposium on Molecular Medicine

Mjesto i datum
Hersonissos, Grčka, 09.10.2008. - 11.10.2008

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cisplatin; resistance; cell adhesion; integrins; cadherins; catenins

Sažetak
Greater insight into the molecular mechanisms regarding modulation of the cellular response to anti-cancer drugs could help to optimize therapeutic strategies. New data suggest the possible role of cell adhesion proteins in drug-resistance. From laryngeal carcinoma HEp2 cells, we have developed cDDP-resistant CA3ST (by cDDP acute treatment) and CK2 (by cDDP chronic treatment) sublines which exhibited altered cell adhesion to extracellular matrix and altered formation of cell-cell junctions comparing to their parental cells. In CA3ST cells we found increased expression of  v 3 integrin and coxsackie adenovirus receptor (CAR). Conversely, in CK2 cells the expression of  v 3 integrin was similar to HEp2, while the expression of CAR was slightly decreased. Both, CA3ST and CK2 sublines showed similar alterations in cell-cell junction proteins, i.e. increased expression of  -catenin and decreased expression of plakoglobin, while the expression of N-cadherin, p120 catenin and desmoglein was similar as compared to HEp2 cells. The isolation of  v 3-expressing stable transfectants from HEp2 cells expressing increased amount of  v 3 integrin, confirmed its role in resistance. However, in HEp2-derived CAR-expressing clones no correlation between CAR expression and cDDP-resistance was found. To show the causative relationship between the pattern of plakoglobin/β -catenin expression and resistance, we overexpressed plakoglobin in CA3ST cells ; yet none of the clones, showing similar plakoglobin/β -catenin pattern to HEp2 cells, restored sensitivity to cisplatin. Thus, increased expression of  v 3 is very likely one of the mechanisms involved in cDDP-resistance. On the contrary, the changes in expression of CAR, plakoglobin and β -catenin expression are presumably a secondary event of cellular response triggered by cisplatin. Therefore, different treatment schedule used for resistance development had induced different alterations in these cells, which are reflected in different resistance-mechanisms.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA