engleski

α vβ 3 INTEGRIN MEDIATED DRUG RESISTANCE IN HUMAN TONGUE SQUAMOUS CELL CARCINOMA

Integrin-mediated drug resistance is based on the adherence of cells to extracellular matrix proteins through integrins. Integrins are cell surface heterodimeric receptors that mediate cell-extracellular matrix adhesion. They influence cell survival by modifying cellular response to chemotherapeutic drugs through mechanisms such as inhibition of apoptosis, decreased cellular proliferation and infl uence the expression of differentiation-regulated genes. We have recently described in human laryngeal carcinoma cells a novel mechanism of multidrug resistance mediated by α vβ 3 integrin, involving glutathione dependent increased ability of α vβ 3 expressing cells to eliminate drug induced ROS. In the present study we investigated whether similar mechanism exist in a different cell model. We used tongue squamous carcinoma cells (Cal27), which express a small amount of α vβ 3 integrins, and Cal27-derived stable transfectants with increased amount of α vβ 3 integrin expression. The cell clones were produced by stable transfection of Cal27 cells with a plasmid expressing the β 3 subunit. Using flow cytometry we measured the expression of α vβ 3 and α vβ 5 in these cell lines in order to verify whether the expression of α vβ 3 decreased the expression of other α v integrins due to the competition of β 3 for available α v. In one stable transfectant the expression of α vβ 3 was increased but the expression of α vβ 5 remained the same in comparison to parental cell line. The other stably transfected cell line showed an increase in α vβ 3 expression and a moderate decrease in α vβ 5 expression. The sensitivity of Cal27 and Cal27-derived α vβ 3 integrin expressing clones to anti cancer drug was determined using MTT assay. Our results showed that both Cal27-derived α vβ 3 integrin expressing cell lines were resistant to cis-diamminedichloroplatinum (cisplatin), doxorubicin and mitomycine C. Since the resistance mechanism of human laryngeal carcinoma cells with inceased α vβ 3 integrin expression is mediated by glutathione, it is now our aim to show whether or not this is also the case with Cal27 cells. Our findings that α vβ 3 integrin mediates resistance in different cell types may have important therapeutic implications. Namely, this integrin is involved in adenovirus transduction ; i.e. for cells that are infected more efficiently, a lower dose of adenovirus vector can achieve the same therapeutic outcome as a higher dose.

integrin α vβ 3; Cal27; drug resistance

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