title: Sclerostin expression in skeletal sarcomas.
abstract: 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/β-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.
authors: 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.
authors: Jia
authors: J
authors: Shen
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
authors: Carolyn A
authors: CA
authors: Meyers
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
authors: Swati
authors: S
authors: Shrestha
authors: Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
authors: Arun
authors: A
authors: Singh
authors: 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.
authors: Greg
authors: G
authors: LaChaud
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
authors: Vi
authors: V
authors: Nguyen
authors: 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.
authors: Greg
authors: G
authors: Asatrian
authors: Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
authors: Noah
authors: N
authors: Federman
authors: UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, CA 90095.
authors: Nicholas
authors: N
authors: Bernthal
authors: Division of Surgical Oncology, University of California, Los Angeles, CA 90095.
authors: Fritz C
authors: FC
authors: Eilber
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
authors: Sarah M
authors: SM
authors: Dry
authors: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, CA 90095.
authors: Kang
authors: K
authors: Ting
authors: UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, CA 90095; Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
authors: Chia
authors: C
authors: Soo
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Pathology, Johns Hopkins University, Baltimore, MD 21205. Electronic address: awjames@jhmi.ed.
authors: Aaron W
authors: AW
authors: James
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000469:Alkaline Phosphatase / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002812:Chondroma / Q000378:metabolism / Q000473:pathology; D002813:Chondrosarcoma / Q000378:metabolism / Q000473:pathology; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D018213:Neoplasms, Bone Tissue / Q000378:metabolism* / Q000473:pathology; D018215:Osteoblastoma / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D010017:Osteoma, Osteoid / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D060449:Wnt Signaling Pathway
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human; D000469:Alkaline Phosphatase
keywords: Chondrosarcoma; Enchondroma; Osteosarcoma; SOST; Sarcoma; Wnt signaling