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

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.