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.