EFFECTS OF HUMAN TUMOR-CELL LINES ON LOCAL NEW BONE-FORMATION IN-VIVO

Although some tumors cause osteolytic lesions, there are some that sti mulate new bone formation. This is an important phenomenon because the responsible mechanisms probably represent an aberration of normal phy siological bone formation, and identifying the factors involved in the process may lead to new therapies for various bone diseases. To clari fy our understanding of the potential mechanism responsible, we compar ed and quantitated the extent of new bone formation stimulated by huma n tumors (HeLa, Hep-2, AV-3, FL, WISH and KB), some of which have oste ogenic activity in vivo [2]. Tumor cells were injected over the calvar ia of nude mice to examine formation of new bone. The tumor cells prod uced three histologically distinct patterns of new bone growth: (1) WI SH and KB stimulated appositional bone growth adjacent to periosteal b one surfaces; (2) HeLa and Hep2 induced new bone growth over calvarial surface even when distant from the tumor mass; (3) FL stimulated bone formation adjacent to periosteum as well as ectopic bone formation in sites distant from bone. All tumors except AV3 induced mean new bone thickness >100 mu m, and Hep-2 cells produced bone 330 mu m thick. PCR and Northern blot analysis of mRNA isolated from cultured tumor cells revealed that all cell lines expressed mRNA for TGF beta, (fibroblast growth factor) FGF-1, FGF-2, and IGF-I, and most cell lines produced mRNA for PDGF. Only FL expressed large amounts of mRNA for BMP2. In se rum-free conditioned media from Hep2 and HeLa cells purified by hepari n affinity chromatography, we have identified FGF-1, FGF-2, and PDGF b y immunodetection with specific antibodies. Our results show that new bone growth caused by these tumors is likely due to the production of bone growth factors by the tumor cells, and that the overall effects o n bone may be due to several factors working in concert.