Spindle‐shaped cells derived from giant‐cell tumor of bone support differentiation of blood monocytes to osteoclast‐like cells

Abstract

Spindle-shaped cells were established from four giant-cell tumors of bone. When human blood monocytes were co-cultured with these cells, multinucleated giant-cell formation of monocytes was induced. Intriguingly, even when a filter (pore size: 0.45 microm) was interposed between monocytes and the spindle-shaped cells, polykaryocytes also appeared. These multinucleated giant cells were positive for tartrate-resistant acid phosphatase, expressed calcitonin receptor, and showed bone-resorption activity, characteristics of osteoclast-like cells. These findings indicate that soluble factors secreted from these cells play an important role in osteoclast-like cell formation from blood monocytes. These data additionally suggest that these cells support osteoclast-like cell formation in giant-cell tumors of bone. The cells also expressed mannose receptor, fibronectin, receptor activator of nuclear factorkappaB, and several cytokine mRNAs, including interleukin-6, receptor activator of nuclear factorkappaB ligand/osteoclast differentiation factor/osteoprotegerin ligand, and macrophage colony-stimulating factor. However, all of these molecules except receptor activator of nuclear factorkappaB ligand mRNA could also be detected in control HeLa and CV-1 cells. Although the soluble receptor activator of nuclear factorkappaB ligand has not been found under physiological conditions, it is possible that it is cleaved by cellular proteases and the truncated receptor activator of nuclear factorkappaB is released from cells. Identification of the soluble factors capable of inducing osteoclast formation from blood monocytes is a pressing problem to be solved.

Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclast formation of human blood monocytes without cell to cell contact

“…In addition, Yasuda et al [33] reported that ODF is the mediator of cell-to-cell interaction. In our previous study [22], the cell-to-cell contact between GCTSC and monocytes was mandatory for osteoclastogenesis in vitro. However, it's currently become clear that soluble mediator can drive osteoclastogenesis in the absence of stromal cells, osteoblasts, or other supporting cells [21].…”

“…After several passages, the multinucleated giant cells and monocytes/macrophage-like round cells progressively disappeared from the cultures, and the proliferating stromal-like cells (GCTSC) only were present after about 4 weeks. Some properties of GCTSC were described previously [22]. These cells were cultured with Dulbecco's minimum essential medium (DMEM) fortified with 5% fetal calf serum (FCS).…”

“…Histologically, it is characterized by a large number of multinucleated giant cells and macrophage-like and stromal cell-like mononuclear cells [2,8,7,13,15,32] . A significant number of macrophages were found to infiltrate t o GCT, and it is generally thought that the multinucleated giant cells are formed from mononuclear phagocytic precursors by cell fusion or nuclear multiplication without cell division [3,5,61. In our previous study [22], the stromal cells derived peripheral blood monocytes were cocultured with GCTSC, the multinucleated giant cell formation of monocytes was induced. These multinucleated giant cells exhibited tartrate-resistant acid phosphatase (TRAP) positive, expressed calcitonin receptor and showed bone resorption activity, indicating that the multinucleated giant cells have characters as osteoclast-like cells.…”

Histogenetic Characterization of Giant Cell Tumor of Bone

“…SC were therefore believed the most likely candidate neoplastic elements of GCT, partly based on their ability to grow both in vitro and in vivo [2,24]. SC exhibit markers of osteogenic differentiation [36,46] and are able to stimulate osteoclasts [34,37] through the ligand for receptor activator of nuclear factor kB (RANKL) [20,28,38], a growth factor essential for the recruitment of osteoclasts by osteoblasts under physiological conditions [18]. In agreement with a putative osteogenic origin of SC, osteoid foci may be found both inside and at the periphery of GCT [8,41], and bone formation, but no evidence of osteoclastogenesis has been observed in immunodeficient mice after subcutaneous injection of GCT tissue or cells [2,24].…”

Giant cell tumor of bone: current review of morphological, clinical, radiological, and therapeutic characteristics

“…The spindle-like stromal cells are the main neoplastic component of GCTB and have been shown to express and secrete a variety of chemotactic factors to enlist pathologic components [12,14,21]. They play an important role in the formation of giant multinucleated cells [7,8,14,17].…”