Downregulation of bone morphogenetic protein receptor 2 promotes the development of neuroblastoma
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai (China)
- Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, Jiangsu (China)
- Fudan University Shanghai Cancer Center, Shanghai (China)
- Department of General Surgery, Jiangxi Children's Hospital, Nanchang, Jiangxi (China)
- Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China)
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. - Highlights: • BMPR2 expression was downregulated in primary NB and was more signifcant in high grade NB. • BMPR2 expression was accompanied by the decrease of NB markers ferritin and enolase. • Enforced expression of BMPR2 decreased proliferation and colony formation ability of cultured NB cells. • Knockdown of BMPR2 led to increased cell growth, clonality and tumorigenicity in mice. • Patients with NB expressing higher level of BMPR2 had significant better overall survival than those with low level.
- OSTI ID:
- 22696841
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 483, Issue 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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