Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In this study, we examined the expression of bone morphogenetic protein receptor 2 (BMPR2) in primary NB and adjacent non-tumor samples (adrenal gland). BMPR2 expression was significantly downregulated in NB tissues, particularly in high-grade NB, and was inversely related to the expression of the NB differentiation markers ferritin and enolase. The significance of the downregulation was further explored in cultured NB cells. While enforced expression of BMPR2 decreased cell proliferation and colony-forming activity, shRNA-mediated knockdown of BMPR2 led to increased cell growth and clonogenicity. In mice, NB cells harboring BMPR2 shRNA showed significantly increased tumorigenicity compared with control cells. We also performed a retrospective analysis of NB patients and identified a significant positive correlation between tumor BMPR2 expression and overall survival. These findings suggest that BMPR2 may play an important role in the development of NB. (C) 2016 Elsevier Inc. All rights reserved.
[1]Fudan Univ, Childrens Hosp, Dept Pediat Surg, Shanghai Key Lab Birth Defects, Shanghai, Peoples R China.
[2]Minist Hlth, Key Lab Neonatal Dis, Shanghai, Peoples R China.
[3]Chinese Acad Med Sci, Ctr Syst Med, Suzhou Inst Syst Med, Suzhou, Jiangsu, Peoples R China.
[4]Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China.
[5]Jiangxi Childrens Hosp, Dept Gen Surg, Nanchang, Jiangxi, Peoples R China.
[6]Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Colorectal & Anal Surg, Shanghai, Peoples R China.
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