Gene expression of monocyte chemoattractant protein-1 in giant cell tumors of bone osteoclastoma: Possible involvement in CD68+ macrophage-like cell migration

Abstract

Giant cell tumor of bone (GCT) is one of a few neoplasms in which the macrophage/osteoclast precursor cells and osteoclast-like giant cells infiltrate the tumor mass. Monocyte chemoattractant protein 1 (MCP-1) is a potent chemotactic factor specific for monocytes. In search of relevant cytokines that may enhance the recruitment of these reactive cells, we evaluated the localization and regulation of MCP-1 mRNA and protein in GCT by using Northern blot analysis, in situ hybridization and immunohistochemistry. We also determined whether conditioned medium obtained from GCT cultures can recruit human peripheral blood monocytes (CD68+) in an in vitro chemotactic assay. Using Northern blot analysis, we detected the specific gene transcript for MCP-1 in all GCT samples tested. In situ hybridization and immunohistochemistry revealed that both MCP-1 gene transcript and protein were consistently present in the cytoplasm of stromal-like tumor cells of GCT. Treatment of mononuclear cells from GCT at third passage with TGF-beta1 for 24 h increased the level of MCP-1 mRNA in a dose-dependent manner, with the maximum effect at 1 ng/ml. Conditioned media from GCT cultures promoted the chemotactic migration of CD68+ peripheral monocytes, an activity which was abolished by the addition of MCP-1 antibody to the conditioned medium. Thus, the results of this study suggest that recruitment of CD68+ macrophage-like cells may be due to the production MCP-1 by stromal-like tumor cells. These CD68+ cells may originate from peripheral blood and could have the capability of further differentiating into osteoclasts in the tumor.

Proliferating cell nuclear antigen labelling index in localised pigmented villo-nodular synovitis and its relationship to the size of nodules

“…A similar mechanism has been recently demonstrated in another tumour [34] and the abundant production of monocyte chemo-attractant protein 1, which is a chemotactic factor specific for monocytes, has been demonstrated in cultures of giant cell tumour of bone, which is a tumour with histological, ultrastructural and immunohistochemical characteristics similar to PVNS.…”

Giant Cell Reparative Granuloma of the Temporal Bone: Neuroradiological and Immunohistochemical Findings. Case Report.

“…GCRG contains much more fibrous stroma, hemosiderin deposits, infiltrative lymphocytes, and reactive bone formation compared with GCT, and the giant cells of GCRG tend to arrange focally and have a smaller number of nuclei than those of GCT. 1,5,17,22,24,34,37,41) Multinucleated giant cells of extracranial GCT and GCRG are immunohistochemically positive for CD68, 2,3,13,16,18,20,21,28,31,32,40,42) suggesting histiocytic differentiation. Similar findings are reported for GCT 7,15) and GCRG 26) of the skull.…”

Giant cell tumor of the uterus: case report and response to chemotherapy

“…Usually GCT is a primary osteolytic bone neoplasm in which monocytic macrophage/osteoclast precursor cells and multinucleated osteoclast-like giant cells infiltrate the tumor [1][2][3]6]. These multinucleated giant cells have biochemical and functional characteristics of osteoclasts (reviewed in [18]).…”

“…The etiology of GCT is unknown, however the tumor cells of GCT have been reported to produce chemoattractants that can recruit osteoclasts and osteoclast precursors [3,6].…”