Otpornost na citostatike posredovana integrinom αvβ3 u stanicama pločastog epitela jezika

master's thesis

• Title (english): αvβ3 integrin mediated drug resistance in human tongue squamous cell carcinoma
• Author: Nikolina Stojanović
• Mentor: Andreja Ambriović Ristov (mentor)
• Committee member: Andreja Ambriović Ristov (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Željka Vidaković Cifrek (član povjerenstva)
• Committee member: Dubravka Hranilović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2009, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Otpornost posredovana integrinom temelji se na prihvaćanju stanica za proteine izvanstaničnog matriksa putem integrina. Na modelu ljudskih stanica karcinoma grkljana opisan je mehanizam otpornosti na citostatike posredovan αvβ3 integrinom. U ovom radu istražili smo postoji li sličan mehanizam i u modelu ljudskih stanica karcinoma pločastog epitela jezika (Cal27). U tu svrhu Cal27 stanice transficirali smo plazmidom koji sadrži β3 podjedinicu i izdvojili smo stabilne transfektante koji eksprimiraju povećanu količinu αvβ3 integrina u usporedbi s roditeljskim Cal27 stanicama. Kod jednog je stabilnog transfektanta ekspresija αvβ3 integrina bila povećana dok je ekspresija αvβ5 integrina ostala jednaka u usporedbi s roditeljskim Cal27 stanicama. Kod drugog transfektanta je došlo do povećanja ekspresije αvβ3 integrina i umjerenog smanjenja ekspresije αvβ5 integrina zbog kompeticije β3 podjedinice za raspoložive αv podjedinice. Osjetljivost roditeljskih Cal27 i odabranih Cal27-αvβ3 integrin stabilnih transfektanata na citostatike određena je MTT testom. Pokazali smo da su oba Cal27 klona otporna na cisplatinu, doksorubicin i mitomicin C. Ovaj rad pokazuje da povećana ekspresija αvβ3 integrina može zaštititi stanice od djelovanja različitih citostatika. Prema tome mjerenje ekspresije αvβ3 integrina u stanicama karcinoma glave i vrata bi mogao biti važan pokazatelj otpornosti tumora na citostatike.

Abstract (english)

Integrin-mediated drug resistance is based on the adherence of cells to extracellular matrix proteins through integrins. In human laryngeal carcinoma cells a mechanism of multidrug resistance mediated by αvβ3 integrin have been described. In the present study we investigated whether similar mechanism exists in tongue squamous carcinoma cells (Cal27) which express a small amount of αvβ3 integrins, and Cal27-derived stable transfectants with increased expression of αvβ3 integrin. The cell clones were produced by stable transfection of Cal27 cells with a plasmid expressing the β3 subunit. In one stable transfectant the expression of αvβ3 was increased but the expression of αvβ5 remained the same in comparison to parental cell line. The other stably transfected cell line showed an increase in αvβ3 expression and a moderate decrease in αvβ5 expression, due to the competition of β3 for available αv in the cell. The sensitivity of Cal27 and Cal27-derived αvβ3 integrin expressing clones to anti cancer drugs was determined using MTT assay. Our results showed that both Cal27-derived αvβ3 integrin expressing cell lines were resistant to cisplatin, doxorubicin and mitomycine C. This thesis shows that increased αvβ3 integrin expression can protect cells from various citostatics. Thus measuring the expression of αvβ3 integrin in head and neck cancer cells could be an important indicator of tumor resistance to anti-cancer drugs.

• Keywords: karcinom pločastog epitela jezika; αvβ3 integrin; otpornost; cisplatina; mitomicin C; doksorubicin; citostatici
• Keywords (english): human tongue squamous cell carcinoma; αvβ3 integrin; otpornost; cisplatin; mitomicin C; doxorubicin; citostatics
• Language: croatian
• URN:NBN: urn:nbn:hr:217:243470
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-16 12:52:38