TY - JOUR
T1 - Gene expression of transforming growth factor-β1 and its type II receptor in giant cell tumors of bone
T2 - Possible involvement in osteoclast-like cell migration
AU - Zheng, Ming H.
AU - Fan, Ying
AU - Wysocki, Stan J.
AU - Lau, Angeline T.T.
AU - Robertson, Terry
AU - Beilharz, Manfred
AU - Wood, David J.
AU - Papadimitriou, John M.
PY - 1994/11
Y1 - 1994/11
N2 - Giant cell tumor of bone (GCT) is a relatively rare skeletal neoplasm characterized by multinuclear giant cells (osteoclast-like cells) scattered in a mass of mononuclear cells. The currently favored hypothesis for the origin of cells within GCT is that the multinuclear giant cells are reactive osteoclasts, whereas the truly neoplastic cells are the major component of the mononuclear population. However, the pathological significance and the precise relationship of tumor cells and osteoclast-like cells in GCT have not been fully established. In this study, we evaluated two GCTs for the presence of transforming growth factor-β1 (TGF-β1) and TGF-β type II receptor gene transcripts and attempted to establish a possible role for TGF-β1 in the interaction between tumor cells and osteoclast-like cells. By using in situ hybridization and Northern blot analysis, we have demonstrated that TGF-β1 mRNA transcript is consistently detected in both tumor mononuclear cells and osteoclast-like cells, whereas TGF-β type II receptor gene transcript is only present in osteoclast-like cells. Moreover, isolated rat osteoclasts were tested for their ability to migrate in response to GCT-conditioned medium (GCTCM) in an in vitro chemotactic assay. Our results showed that GCTCM stimulates the migration of osteoclasts in a dose-dependent manner. Interestingly, only osteoclasts containing less than three nuclei can migrate through 12-μ pore filters. Addition of monoclonal antibody against TGF-β significantly reduced but did not abolish the chemotactic activity of GCTCM. Moreover, TGF-β type II receptor mRNA has been demonstrated in the normal rat osteoclasts and may be involved in the chemotactic action of TGF-β1. We concluded that TGF-β1, possibly in concert with other cytokines, is involved in the recruitment of osteoclast-like cells in GCT by acting in an autocrine or paracrine fashion.
AB - Giant cell tumor of bone (GCT) is a relatively rare skeletal neoplasm characterized by multinuclear giant cells (osteoclast-like cells) scattered in a mass of mononuclear cells. The currently favored hypothesis for the origin of cells within GCT is that the multinuclear giant cells are reactive osteoclasts, whereas the truly neoplastic cells are the major component of the mononuclear population. However, the pathological significance and the precise relationship of tumor cells and osteoclast-like cells in GCT have not been fully established. In this study, we evaluated two GCTs for the presence of transforming growth factor-β1 (TGF-β1) and TGF-β type II receptor gene transcripts and attempted to establish a possible role for TGF-β1 in the interaction between tumor cells and osteoclast-like cells. By using in situ hybridization and Northern blot analysis, we have demonstrated that TGF-β1 mRNA transcript is consistently detected in both tumor mononuclear cells and osteoclast-like cells, whereas TGF-β type II receptor gene transcript is only present in osteoclast-like cells. Moreover, isolated rat osteoclasts were tested for their ability to migrate in response to GCT-conditioned medium (GCTCM) in an in vitro chemotactic assay. Our results showed that GCTCM stimulates the migration of osteoclasts in a dose-dependent manner. Interestingly, only osteoclasts containing less than three nuclei can migrate through 12-μ pore filters. Addition of monoclonal antibody against TGF-β significantly reduced but did not abolish the chemotactic activity of GCTCM. Moreover, TGF-β type II receptor mRNA has been demonstrated in the normal rat osteoclasts and may be involved in the chemotactic action of TGF-β1. We concluded that TGF-β1, possibly in concert with other cytokines, is involved in the recruitment of osteoclast-like cells in GCT by acting in an autocrine or paracrine fashion.
UR - http://www.scopus.com/inward/record.url?scp=0027944956&partnerID=8YFLogxK
M3 - Article
C2 - 7977641
AN - SCOPUS:0027944956
SN - 0002-9440
VL - 145
SP - 1095
EP - 1104
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -