NELL-1 expression in benign and malignant bone tumors

Shen, Jia; LaChaud, Greg; Khadarian, Kevork; Shrestha, Swati; Zhang, Xinli; Ting, Kang; Dry, Sarah M.; James, Aaron W.

doi:10.1016/j.bbrc.2015.03.040

Cited by 13 publications

(21 citation statements)

References 27 publications

(18 reference statements)

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“…For example, NELL-1 has been found to be epigenetically silenced via methylation in several carcinomas, including colon adenocarcinoma, 26 esophageal adenocarcinoma, 27 as well as renal cell carcinoma. 28 Our study, in combination with our previous observations, 25 suggests that the opposite is true in skeletal sarcomas, including consistent NELL-1 overexpression in both osteosarcoma and chondrosarcoma. The bioactive effects of NELL-1 in skeletal sarcomas remain a matter of speculation; however, recent understanding of NELL-1 as an integrin b1 ligand may reveal new insights.…”

Section: Discussionsupporting

confidence: 81%

“…Overall a qualitative increase in staining among chondroblastic areas with increasing cellularity was observed, consistent with our prior observations. 25 However, some element of NELL-1 staining was observed in each tumor sample.…”

Section: Nell-1 Expression In Chondroblastic Osteosarcomamentioning

confidence: 90%

“…Recently, we reported the expression patterns of NELL-1 in benign and malignant bone tumors. 25 Briefly, we found that among benign bone tumors (osteoid osteoma and osteoblastoma), strong and diffuse NELL-1 expression 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.…”

mentioning

confidence: 89%

“…Intensity and distribution of immunohistochemical staining were determined by three blinded observers, as previously performed. 25 The intensity of staining was estimated using a 3 point scale, with '0 0 indicating no staining, '1+' indicating predominantly faint/barely perceptible cytoplasmic staining within any percentage of tumor cells, '2+' indicating predominantly weak/moderate cytoplasmic staining within any percentage of tumor cells, and '3+' indicating strong/intense cytoplasmic staining within any percentage of tumor cells. Discrepancies in semi-quantification of intensity of staining between observers were found in <10% of samples.…”

Section: Histological and Immunohistochemical Analysesmentioning

confidence: 99%

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NELL-1 expression in tumors of cartilage

Shen

LaChaud

Shrestha

et al. 2015

Journal of Orthopaedics

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Section: Discussionsupporting

confidence: 81%

Section: Nell-1 Expression In Chondroblastic Osteosarcomamentioning

confidence: 90%

mentioning

confidence: 89%

Section: Histological and Immunohistochemical Analysesmentioning

confidence: 99%

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NELL-1 expression in tumors of cartilage

Shen

LaChaud

Shrestha

et al. 2015

Journal of Orthopaedics

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“…NELL-1 has documented tumor-suppression properties and its expression is lost in several carcinomas (32,33). Recently, we documented high expression of NELL-1 among several bone-and cartilage-forming tumors, but its expression does not correlate with benign and malignant tumor types (34,35). Finally, NELL-1 has an excellent safety profile.…”

Section: Cd31mentioning

confidence: 97%

NELL-1 induces Sca-1+ mesenchymal progenitor cell expansion in models of bone maintenance and repair

James¹,

Shen²,

Tsuei³

et al. 2017

JCI Insight

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Nell‐1‐ΔE, a novel transcript of Nell‐1, inhibits cell migration by interacting with enolase‐1

Zhao

Qin

Zhang

et al. 2018

J of Cellular Biochemistry

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NELL-1 is a secreted protein that was originally found to be upregulated in pathologically fusing and fused sutures in non-syndromic unilateral coronal synostosis patients. Apart from the ability of NELL-1 to promote osteogenesis in long and craniofacial bones, NELL-1 reportedly inhibits the formation of several benign and malignant tumors. We previously identified a novel transcript of Nell-1 that lacked a calcium-binding epidermal growth factor (EGF)-like domain compared with full-length Nell-1; this new transcript was named Nell-1-ΔE. Three obvious structural differences between these two isoforms were revealed by homology modeling. Furthermore, the recombinant Nell-1-ΔE protein, but not the full-length Nell-1 protein, inhibited cell migration in vitro. However, full-length Nell-1 and Nell-1-ΔE proteins were present in similar subcellular locations and displayed similar expression patterns in both the intracellular and extracellular spaces. The results from the co-immunoprecipitation and liquid chromatography/tandem mass spectrometry analyses using two cell lines demonstrated that Nell-1-ΔE but not full-length Nell-1 interacted with enolase-1 in the extracellular spaces of both cell lines. The results of wound healing assays using ENO-1-overexpressing cells treated with full-length Nell-1/Nell-1-ΔE suggested that Nell-1-ΔE inhibited cell migration by interacting with ENO-1. Our study indicated that the novel transcript Nell-1-ΔE, but not full-length Nell-1, might be a candidate tumor suppressor factor for basic research and clinical practice.

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NELL-1 expression in benign and malignant bone tumors

Cited by 13 publications

References 27 publications

NELL-1 expression in tumors of cartilage

NELL-1 expression in tumors of cartilage

NELL-1 induces Sca-1+ mesenchymal progenitor cell expansion in models of bone maintenance and repair

Nell‐1‐ΔE, a novel transcript of Nell‐1, inhibits cell migration by interacting with enolase‐1

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