[PMID]: | 27498059 |
[Au] Autor: | Shen J; Meyers CA; Shrestha S; Singh A; LaChaud G; Nguyen V; Asatrian G; Federman N; Bernthal N; Eilber FC; Dry SM; Ting K; Soo C; James AW |
[Ad] Endereço: | Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, CA 90095; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095. |
[Ti] Título: | Sclerostin expression in skeletal sarcomas. |
[So] Source: | Hum Pathol;58:24-34, 2016 Dec. |
[Is] ISSN: | 1532-8392 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Sclerostin (SOST) is an extracellular Wnt signaling antagonist which negatively regulates bone mass. Despite this, the expression and function of SOST in skeletal tumors remain poorly described. Here, we first describe the immunohistochemical staining pattern of SOST across benign and malignant skeletal tumors with bone or cartilage matrix (n=68 primary tumors). Next, relative SOST expression was compared to markers of Wnt signaling activity and osteogenic differentiation across human osteosarcoma (OS) cell lines (n=7 cell lines examined). Results showed immunohistochemical detection of SOST in most bone-forming tumors (90.2%; 46/51) and all cartilage-forming tumors (100%; 17/17). Among OSs, variable intensity and distribution of SOST expression were observed, which highly correlated with the presence and degree of neoplastic bone. Patchy SOST expression was observed in cartilage-forming tumors, which did not distinguish between benign and malignant tumors or correlate with regional morphologic characteristics. Finally, SOST expression varied widely between OS cell lines, with more than 97-fold variation. Among OS cell lines, SOST expression positively correlated with the marker of osteogenic differentiation alkaline phosphatase and did not correlate well with markers of Wnt/ß-catenin signaling activity. In summary, SOST is frequently expressed in skeletal bone- and cartilage-forming tumors. The strong spatial correlation with bone formation and the in vitro expression patterns are in line with the known functions of SOST in nonneoplastic bone, as a feedback inhibitor on osteogenic differentiation. With anti-SOST as a potential therapy for osteoporosis in the near future, its basic biologic and phenotypic consequences in skeletal tumors should not be overlooked. |
[Mh] Termos MeSH primário: |
Biomarcadores Tumorais/metabolismo Proteínas Morfogenéticas Ósseas/metabolismo Neoplasias Ósseas/metabolismo Neoplasias de Tecido Ósseo/metabolismo
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[Mh] Termos MeSH secundário: |
Fosfatase Alcalina/metabolismo Biópsia Neoplasias Ósseas/patologia Diferenciação Celular Linhagem Celular Tumoral Condroma/metabolismo Condroma/patologia Condrossarcoma/metabolismo Condrossarcoma/patologia Marcadores Genéticos Seres Humanos Imuno-Histoquímica Neoplasias de Tecido Ósseo/patologia Osteoblastoma/metabolismo Osteoblastoma/patologia Osteogênese Osteoma Osteoide/metabolismo Osteoma Osteoide/patologia Osteossarcoma/metabolismo Osteossarcoma/patologia Estudos Retrospectivos Via de Sinalização Wnt
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Biomarkers, Tumor); 0 (Bone Morphogenetic Proteins); 0 (Genetic Markers); 0 (SOST protein, human); EC 3.1.3.1 (Alkaline Phosphatase) |
[Em] Mês de entrada: | 1708 |
[Cu] Atualização por classe: | 170828 |
[Lr] Data última revisão:
| 170828 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 160808 |
[St] Status: | MEDLINE |
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