title: Neuropilin-2 expression is inhibited by secreted Wnt antagonists and its down-regulation is associated with reduced tumor growth and metastasis in osteosarcoma.
abstract: BACKGROUND
  Neuropilin 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.
  
  
  RESULTS
  NRP2 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.
  
  
  CONCLUSIONS
  Regulation 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.
authors.affiliation: Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. jitaomd@163.com.|Musculoskeletal Tumor Center, People's Hospital, Peking University, Beijing, China. jitaomd@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Ji
authors.affiliation: Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. guoyidr@gmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. Kimkapj@yahoo.com.
authors.forename: Kapjun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. mcqueenp@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: McQueen
authors.affiliation: Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. ghaffarsa@yahoo.com.
authors.forename: Samia
authors.initials: S
authors.lastname: Ghaffar
authors.affiliation: Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. alexander.b.christ@gmail.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Christ
authors.affiliation: Department of Oncology, CHOC Children's Hospital, Orange, CA, USA. carolhhwang@yahoo.com.
authors.forename: Carol
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, University of California, Irvine, CA, USA. eskander@uci.edu.
authors.forename: Ramez
authors.initials: R
authors.lastname: Eskander
authors.affiliation: Department of Urology and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. zix@uci.edu.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zi
authors.affiliation: Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. bahoang@montefiore.org.|Department of Orthopaedic Surgery, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, 3400 Bainbridge Ave, 6th Floor, Bronx, NY, 10476, USA. bahoang@montefiore.org.
authors.forename: Bang H
authors.initials: BH
authors.lastname: Hoang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics; D039943:Neuropilin-2 / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D060449:Wnt Signaling Pathway
chemical_list: D039943:Neuropilin-2; D034741:RNA, Small Interfering; D051153:Wnt Proteins