title: Malignant B-lymphoid cells with bone lesions express receptor activator of nuclear factor-kappaB ligand and vascular endothelial growth factor to enhance osteoclastogenesis.
abstract: OBJECTIVE
  Receptor activator of nuclear factor-kappaB ligand (RANKL) is a key mediator of osteoclastogenesis. Because certain types of tumor cells aberrantly express RANKL, and because bone destruction also develops in B-cell lymphomas of bone origin, we investigated RANKL expression and the mechanisms of osteoclastogenesis in B-lymphoid neoplasms.
  
  
  RESULTS
  Immunohistochemistry of bone specimens resected from patients with primary B-cell lymphoma of bone with bone destruction revealed that lymphoma cells express RANKL as well as vascular endothelial cell growth factor (VEGF). The tumor cells isolated from the bone specimens enhanced osteoclastogenesis in vitro. In contrast, B-cell lymphoma infiltrating to the bone marrow without bone destruction did not express RANKL. Both RANKL and VEGF were expressed by a portion of B-lymphoid cell lines, including Daudi and IM-9. These RANKL-expressing tumor cells enhanced osteoclastogenesis from RAW264.7 cells and human monocyte-derived preosteoclasts in the absence of stromal cells/osteoblasts in a RANKL-dependent manner. Furthermore, conditioned media from Daudi cells enhanced transmigration of preosteoclasts that was inhibited by anti-VEGF antibody, suggesting that tumor cell-derived VEGF mediates recruitment of osteoclast precursors. Moreover, cocultures of B-lymphoid cell lines with osteoclasts enhanced the growth of B-lymphoid cells.
  
  
  CONCLUSIONS
  Some malignant B cells aberrantly express functional RANKL as well as VEGF to enhance osteoclastogenesis. The coexpression of RANKL and VEGF may also contribute to the close cellular interactions with osteoclastic cells, thereby forming a vicious cycle between osteoclastic bone destruction and tumor expansion in bone.
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Shibata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Abe
authors.forename: Kenji
authors.initials: K
authors.lastname: Hiura
authors.forename: Javier
authors.initials: J
authors.lastname: Wilde
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sano
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kitazoe
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Ozaki
authors.forename: Shingo
authors.initials: S
authors.lastname: Wakatsuki
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kido
authors.forename: Daisuke
authors.initials: D
authors.lastname: Inoue
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement; D017077:Culture Media, Conditioned; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A