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Targeting the giant cell tumor stromal cell: functional characterization and a novel therapeutic strategy.
- Source :
-
PloS one [PLoS One] 2013 Jul 26; Vol. 8 (7), pp. e69101. Date of Electronic Publication: 2013 Jul 26 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Giant cell tumor of bone (GCTB) is a benign, locally destructive neoplasm, with tumors comprised of mesenchymal fibroblast-like stromal cells; monocytic, mononuclear cells of myeloid lineage; and the characteristic osteoclast-like, multinucleated giant cells. Hampering the study of the complex interaction of its constituent cell types is the propensity of longstanding, repeatedly passaged cell cultures to undergo phenotypic alteration and loss of osteoclast-inducing capacities. In this study, we employed a novel, single-step technique to purify freshly harvested stromal cells using a CD14-negative selection column. Using 9 freshly harvested GCTB specimens and the purified stromal cell component, we performed analyses for markers of osteoblast lineage and analyzed the capacity of the stromal cells to undergo osteoblastic differentiation and induce osteoclastogenesis in co-cultures with monocytic cells. Successful purification of the CD14-negative stromal cells was confirmed via flow cytometric analysis and immunocytochemistry. Osteogenic media upregulated the expression of osteocalcin, suggesting an osteoblastic lineage of the GCTB stromal cells. The effects of the Wnt pathway agonist, SB415286, and recombinant human bone morphogenetic protein (BMP)-2 on osteoblastogenesis varied among samples. Notably, osteogenic media and SB415286 reversed the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) expression ratio resulting in diminished osteoclastogenic capacity. Recombinant human BMP2 had the opposite effect, resulting in enhanced and sustained support of osteoclastogenesis. Targeting the giant cell tumor stromal cell may be an effective adjunct to existing anti-resorptive strategies.
- Subjects :
- Adolescent
Adult
Aminophenols pharmacology
Aminophenols therapeutic use
Bone Morphogenetic Proteins metabolism
Cell Differentiation drug effects
Cell Separation
Culture Media pharmacology
Female
Giant Cell Tumor of Bone drug therapy
Humans
Ligands
Male
Maleimides pharmacology
Maleimides therapeutic use
Middle Aged
Osteoblasts drug effects
Osteoblasts metabolism
Osteoblasts pathology
Osteoclasts drug effects
Osteoclasts metabolism
Osteoclasts pathology
Osteogenesis drug effects
Osteoprotegerin metabolism
Polymerase Chain Reaction
RANK Ligand metabolism
Stromal Cells
Wnt Signaling Pathway drug effects
Young Adult
Giant Cell Tumor of Bone pathology
Giant Cell Tumor of Bone therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23922683
- Full Text :
- https://doi.org/10.1371/journal.pone.0069101