GENE-EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND ITS TYPE-II RECEPTOR IN GIANT-CELL TUMORS OF BONE - POSSIBLE INVOLVEMENT IN OSTEOCLAST-LIKE CELL-MIGRATION

Giant cell tumor of bone (GCT) is a relatively rare skeletal neoplasm characterized by multinuclear giant cells (osteoclast-like cells) scat tered in a mass of mononuclear cells. The currently favored hypothesis for the origin of cells within GCT is that the multinuclear giant cel ls are reactive osteoclasts, whereas the truly neoplastic cells are th e major component of the mononuclear population. However, the patholog ical significance and the precise relationship of tumor cells and oste oclast-like cells in GCT have not been fully established In this study , we evaluated two GCTs for the presence of transforming growth factor -beta 1 (TGF-beta 1) and TGF-beta type II receptor gene transcripts an d attempted to establish a possible role for TGF-beta 1 in the interac tion between tumor cells and osteoclast-like cells. By using in situ h ybridization and Northern blot analysis, we have demonstrated that TGF -beta 1 mRNA transcript is consistently detected in both tumor mononuc lear cells and osteoclast-like cells, whereas TGF-beta type II recepto r gene transcript is only present in osteoclast-like cells. Moreover, isolated rat osteoclasts were tested for their ability to migrate in r esponse to GCT-conditioned medium (GCTCM) in an in vitro chemotactic a ssay. Our results showed that GCTCM stimulates the migration of osteoc lasts in a dose-dependent manner. Interestingly, only osteoclasts cont aining less than three nuclei can migrate through 12-mu pore filters. Addition of monoclonal antibody against TGF-beta significantly reduced but did not abolish the chemotactic activity of GCTCM. Moreover, TGF- beta type II receptor mRNA has been demonstrated in the normal rat ost eoclasts and may be involved in the chemotactic action of TGF-beta 1. We concluded that TGF-beta 1, possibly in concert with other cytokines , is involved in the recruitment of osteoclast-like cells in GCT by ac ting in an autocrine or paracrine fashion.