NELL-1 expression in benign and malignant bone tumors

Jia Shen, Greg Lachaud, Kevork Khadarian, Swati Shrestha, Xinli Zhang, Chia Soo, Kang Ting, Sarah M. Dry, Aaron W. James

Research output: Contribution to journalArticle

Abstract

NELL-1 (NEL-like Protein 1) is an osteoinductive protein with increasing usage as a bone graft substitute in preclinical animal models. NELL-1 was first identified to have bone-forming properties by its overexpression in fusing cranial sutures. Since this time, addition of recombinant NELL-1 has been used to successfully induce bone formation in the calvarial, axial and appendicular skeleton. With increasing interest in the use of NELL-1 as a bone-graft substitute, we sought to examine the expression of NELL-1 in a wide spectrum of benign and malignant bone-forming skeletal tumors. Immunohistochemical expression was examined in human pathologic specimens. Quantitative RT-PCR evaluated NELL-1 expression among OS cell lines in vitro. Results showed NELL-1 expression in all bone tumors. Likewise, all OS cell lines demonstrated increased NELL-1 expression in comparison to non-lesional human bone marrow stromal cells. Among, benign bone tumors (osteoid osteoma and osteoblastoma), strong and diffuse staining was observed, which spatially correlated with markers of osteogenic differentiation. In contrast, a relative reduction in NELL-1 staining was observed in osteosarcoma, accompanied by increased variation between tumors. Among osteosarcoma specimens, NELL-1 expression did not correlate well with markers of osteogenic differentiation. Surprisingly, among osteosarcoma subtypes, fibroblastic osteosarcoma demonstrated the highest expression of NELL-1. In summary, NELL-1 demonstrates diffuse and reliable expression in benign but not malignant bone-forming skeletal tumors. Future studies will further define the basic biologic, diagnostic and prognostic importance of NELL-1 in bone neoplasms.

Original languageEnglish (US)
Pages (from-to)368-374
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume460
Issue number2
DOIs
StatePublished - May 1 2015
Externally publishedYes

Keywords

  • Nell-1
  • Osteoblastoma
  • Osteoid osteoma
  • Osteosarcoma

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Shen, J., Lachaud, G., Khadarian, K., Shrestha, S., Zhang, X., Soo, C., Ting, K., Dry, S. M., & James, A. W. (2015). NELL-1 expression in benign and malignant bone tumors. Biochemical and Biophysical Research Communications, 460(2), 368-374. https://doi.org/10.1016/j.bbrc.2015.03.040