Gene Expression of Monocyte Chemoattractant Protein-1 in Giant Cell Tumors of Bone Osteoclastoma: Possible Involvement in CD68+ Macrophage-Like Cell Migration

M.H. Zheng, Y. Fan, A. Smith, S. Wysocki, John Papadimitriou, D.J. Wood

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51 Citations (Scopus)

Abstract

Giant cell tumor of bone (CCT) 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 CCT. Treatment of mononuclear cells from GCT at third passage with TGF-beta 1 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. (C) 1998 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)121-129
JournalJournal of Cellular Biochemistry
Volume70
Issue numberN/A
DOIs
Publication statusPublished - 1998

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