Title

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

Date of Award

12-1-2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Cancer Biology

Department

Graduate School of Biomedical Sciences

First Advisor

Andras G. Lacko

Second Advisor

Harlan P. Jones

Third Advisor

Maya P. Nair

Abstract

Neuroblastoma (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.

Comments

Panchoo, Marlyn., Role of Scavenger Receptor Class B Type 1 in High-Risk Neuroblastoma. Doctor of Philosophy (Biochemistry and Cancer Biology), November 2017, 89 pages, 4 tables, 23 figures. Available worldwide December 2018.

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