Expression Profiling of Receptor-Activator of Nuclear Factor-Kappa B Ligand in Soft Tissue Tumors

Access this Article

Search this Article

Author(s)

    • Yamagishi Tetsuro
    • Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences
    • Ajioka Yoichi
    • Histopathology Core Facility, Niigata University Faculty of Medicine|Division of Molecular and Diagnostic Pathology, Niigata University Faculty of Medicine
    • Endo Naoto
    • Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences
    • Kawashima Hiroyuki
    • Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences
    • Ogose Akira
    • Department of Orthopedic Surgery, Uonuma Kikan Hospital
    • Ariizumi Takashi
    • Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences
    • Oike Naoki
    • Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences
    • Sasaki Taro
    • Department of Orthopedic Surgery, Niigata Cancer Center Hospital
    • Hatano Hiroshi
    • Department of Orthopedic Surgery, Niigata Cancer Center Hospital
    • Ohashi Riuko
    • Histopathology Core Facility, Niigata University Faculty of Medicine
    • Umezu Hajime
    • Division of Pathology, Niigata University Medical and Dental Hospital

Abstract

<p>Bone and soft tissue tumors are derived from mesenchymal cells, and they are hard to treat. Receptor-activator of nuclear factor-kappa B ligand (RANKL) is an essential cytokine for osteoclast differentiation and activation and is expressed on the surface of osteoblasts or stromal cells. In this study, to explore the potential of denosumab treatment for soft tissue tumors, we analyzed the expression profiles of RANKL mRNA in 425 tumor specimens of 33 histological types by real-time RT-PCR. Denosumab is a monoclonal antibody that prevents the binding of RANKL to receptor-activator of nuclear factor-kappa B (RANK). For comparison, the relative expression levels of RANK and osteoprotegerin (OPG) mRNAs were also measured. OPG functions as a soluble decoy receptor for RANKL. Higher expression levels of RANKL mRNA were detected in calcifying aponeurotic fibroma, fibrosarcoma, calcifying epithelioma, myositis ossificans, heterotopic calcification, giant cell tumor of the tendon sheath (GCTTS), and pigmented villonodular synovitis (PVNS), compared with the levels of other tumor types. Moreover, the expression levels of RANK mRNA were highest in GCTTS, followed by myositis ossificans and PVNS, whereas the expression levels of OPG mRNA were greatly varied among these histological types. We then analyzed RANKL protein expression by immunohistochemistry in 57 tumor specimens with higher expression levels of RANKL mRNA. RANKL-positive cells were detected in GCTTS, PVNS, myositis ossificans, heterotopic calcification, and calcifying aponeurotic fibroma. In conclusion, RANKL is expressed in subsets of soft tissue tumors with calcification, and denosumab is a potential therapeutic option for soft tissue tumors expressing RANKL.</p>

Journal

  • The Tohoku Journal of Experimental Medicine

    The Tohoku Journal of Experimental Medicine 248(2), 87-97, 2019

    Tohoku University Medical Press

Codes

  • NII Article ID (NAID)
    130007662277
  • Text Lang
    ENG
  • ISSN
    0040-8727
  • Data Source
    J-STAGE 
Page Top