Neuropilin-2 expression is inhibited by secreted Wnt antagonists and its down-regulation is associated with reduced tumor growth and metastasis in osteosarcoma

Molecular Cancer

Research

Ramez Eskander¹  Carol Lin²  Peter McQueen³  Samia Ghaffar³  Kapjun Kim³  Yi Guo³  Alexander Christ³  Bang H Hoang⁴  Tao Ji⁵  Xiaolin Zi⁶ 

[1] Department of Obstetrics and Gynecology, University of California, Irvine, CA, USA;Department of Oncology, CHOC Children’s Hospital, Orange, CA, USA;Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA;Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA;Department of Orthopaedic Surgery, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, 3400 Bainbridge Ave, 6th Floor, 10476, Bronx, NY, USA;Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA;Musculoskeletal Tumor Center, People’s Hospital, Peking University, Beijing, China;Department of Urology and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA;

关键词: Osteosarcoma;    Neuropilin;    Lung metastasis;    Angiogenesis;    Wnt pathway;   

DOI  :  10.1186/s12943-015-0359-4

 received in 2014-09-11, accepted in 2015-04-06,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundNeuropilin 2 (NRP2) isa multi-functional co-receptor to many receptors, including VEGF receptor, c-Met and others. NRP2 has recently been implicated in tumor angiogenesis, growth, and metastasis of many other cancers. However, its role in osteosarcoma remains poorly understood.ResultsNRP2 was overexpressed in osteosarcoma cell lines and tissues, and associated with poor survival of osteosarcoma patients. Knockdown of NRP2 expression by short-hairpin (Sh) RNA resulted in reduced tumor growth, metastasis, and blood vessel formation of osteosarcoma. Knockdown of NRP2 expression by ShRNA also inhibited the recruitment of HUVEC cells to osteosarcoma cells. Inhibition of Wnt signaling by overexpression of secreted Wnt antagonists soluble LRP5, Frzb, and WIF1 markedly down-regulated mRNA and protein expression of NRP2 in osteosarcoma cell lines.ConclusionsRegulation of NRP2 receptor expression may represent a novel approach for treatment of osteosarcoma through retarding osteosarcoma growth, metastasis and blood vessel formation. In addition, down-regulation of NRP2 expression can be achieved by expression of secreted Wnt antagonists.

【 授权许可】

Unknown   
© Ji et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.