Role of Scavenger Receptor Class B Type 1 in High-Risk Neuroblastoma

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dc.contributor.advisorLacko, Andras G.
dc.contributor.committeeMemberJones, Harlan P.
dc.contributor.committeeMemberNair, Maya P.
dc.creatorPanchoo, Marlyn
dc.date.accessioned2019-08-22T20:50:10Z
dc.date.available2019-08-22T20:50:10Z
dc.date.issued2017-12-01
dc.date.submitted2018-05-22T12:18:08-07:00
dc.description.abstractNeuroblastoma (NB), the most common extra-cranial childhood cancer in the United States is responsible for 15% of all pediatric cancer deaths. Due to advancements in treatment approaches, survival in low- and intermediate-risk NB patients now exceeds 90%. However, patient outcome for high-risk NB still remains poor with an overall survival of less than 50%. Nearly all high-risk NB patients present with metastatic disease at diagnosis and are unresponsive to intense chemotherapy, radiotherapy or aggressive surgery. Recently, the high-density lipoprotein (HDL) receptor, scavenger receptor class B type 1 (SR-B1), has emerged as an important indicator of cancer progression and patient outcome. Moreover, cancerous cells exhibit a higher expression of SR-B1 than normal non-malignant cells. SR-B1 is mainly responsible for the selective uptake of cholesteryl ester (CE) from HDL but also mediates reverse cholesterol transport. In this study, the expression of SR-B1 was identified on high-risk NB cells. Blocking of SR-B1 diminished cell proliferation, migration and invasion and induced apoptosis. Additionally, inhibition of SR-B1 reduced CE content in high-risk NB cells. Finally, high expression of SR-B1 in NB biopsy samples correlated with poor patient outcome. Taken together, this study identified SR-B1 expression as a potential regulator of high-risk NB progression linked to changes in cellular cholesterol metabolism. These findings also identify SR-B1 as a potential target for treatment of high-risk NB.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/28824
dc.language.isoen
dc.provenance.legacyDownloads13
dc.subjectMedical Sciences
dc.subjectMedicine and Health Sciences
dc.subjectHigh-risk neuroblastoma
dc.subjectCholesterol metabolism
dc.subjectScavenger receptor class B type1
dc.subjectHigh-density lipoprotein
dc.titleRole of Scavenger Receptor Class B Type 1 in High-Risk Neuroblastoma
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineCancer Biology
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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