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Title: Changes in the ATP-binding cassette efflux transporters of the blood-brain barrier in glioma challenge
Author: Georgian, Ana Ruxandra
ISNI:       0000 0004 6062 0172
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2014
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The ATP-binding cassette (ABC) family of efflux transporters are expressed on the blood-facing (apical) surface of blood-brain barrier (BBB) endothelia and include P- glycoprotein (Pgp) and breast cancer resistance protein (BCRP). These neuro- protective transporters restrict the movement of compounds from the blood to the brain, including many chemotherapeutics; hence make treatment of brain tumours difficult. To further understand the role of efflux transporters in brain cancer, an in vitro model of primary porcine brain endothelial cells (PBECs) was used to explore changes in transporter expression at the BBB in response to glioma challenge. The in vitro results were then compared with changes in ABC transporter expression found within human brain tissue of glioma patients. The activity and expression of Pgp and BCRP in PBECs were compared between PBECs in co-culture with glioma cells (glioma model) and PBECs in co-culture with normal astrocytes (normal model control), to identify any differences in ABC transporters. Further work was conducted to identify any signaling pathways involved in inducing ABC transporter changes during glioma challenge. For this purpose, PBECs were grown in media conditioned by either normal astrocytes or glioma cells, where the function of ABC transporters in response to modulators of Sonic and Wnt signaling was assessed. Finally, confocal microscopy was used to examine the expression of BCRP and Pgp in brain tissue of glioma patients. The results have implication for the delivery of chemotherapeutics to the brain during tumour challenges.
Supervisor: Preston-Kennedy, Jane Elizabeth ; Abbott, Nancy Joan ; Begley, David John Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available