title: NELL-1 expression in benign and malignant bone tumors.
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.
authors: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA.
authors: Jia
authors: J
authors: Shen
authors: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA.
authors: Greg
authors: G
authors: LaChaud
authors: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA.
authors: Kevork
authors: K
authors: Khadarian
authors: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA.
authors: Swati
authors: S
authors: Shrestha
authors: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA.
authors: Xinli
authors: X
authors: Zhang
authors: Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA; UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and The Orthopaedic Hospital Research Center, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA.
authors: Chia
authors: C
authors: Soo
authors: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA.
authors: Kang
authors: K
authors: Ting
authors: Department of Pathology and Laboratory Medicine, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA.
authors: Sarah M
authors: SM
authors: Dry
authors: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA; UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and The Orthopaedic Hospital Research Center, University of California, David Geffen School of Medicine, 10833 Le Conte Ave., 13-145 CHS, Los Angeles, CA 90095, USA. Electronic address: Awjames@mednet.ucla.edu.
authors: Aaron W
authors: AW
authors: James
mesh_terms: D001859:Bone Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins; D045744:Cell Line, Tumor; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012516:Osteosarcoma / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction
chemical_list: D002135:Calcium-Binding Proteins; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins
keywords: Nell-1; Osteoblastoma; Osteoid osteoma; Osteosarcoma