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

Tao Ji, Yi Guo, Kapjun Kim, Peter McQueen, Samia Ghaffar, Alexander Christ, Carol Lin, Ramez Eskander, Xiaolin Zi, Bang H. Hoang

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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.

Original languageEnglish (US)
Article number86
JournalMolecular Cancer
Volume14
Issue number1
DOIs
StatePublished - Apr 17 2015

Fingerprint

Neuropilin-2
Osteosarcoma
Down-Regulation
Neoplasm Metastasis
Growth
Neoplasms
Blood Vessels
Cell Line
Vascular Endothelial Growth Factor Receptor
Human Umbilical Vein Endothelial Cells
Small Interfering RNA

Keywords

  • Angiogenesis
  • Lung metastasis
  • Neuropilin
  • Osteosarcoma
  • Wnt pathway

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Neuropilin-2 expression is inhibited by secreted Wnt antagonists and its down-regulation is associated with reduced tumor growth and metastasis in osteosarcoma. / Ji, Tao; Guo, Yi; Kim, Kapjun; McQueen, Peter; Ghaffar, Samia; Christ, Alexander; Lin, Carol; Eskander, Ramez; Zi, Xiaolin; Hoang, Bang H.

In: Molecular Cancer, Vol. 14, No. 1, 86, 17.04.2015.

Research output: Contribution to journalArticle

Ji, Tao ; Guo, Yi ; Kim, Kapjun ; McQueen, Peter ; Ghaffar, Samia ; Christ, Alexander ; Lin, Carol ; Eskander, Ramez ; Zi, Xiaolin ; Hoang, Bang H. / Neuropilin-2 expression is inhibited by secreted Wnt antagonists and its down-regulation is associated with reduced tumor growth and metastasis in osteosarcoma. In: Molecular Cancer. 2015 ; Vol. 14, No. 1.
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AU - Christ, Alexander

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AU - Eskander, Ramez

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