Effects of human tumor cell lines on local new bone formation in vivo

E. Izbicka, C. R. Dunstan, D. Horn, M. Harris, Stephen E Harris, R. Adams, G. R. Mundy

Research output: Contribution to journalArticle

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Abstract

Although some tumors cause osteolytic lesions, there are some that stimulate new bone formation. This is an important phenomenon because the responsible mechanisms probably represent an aberration of normal physiological bone formation, and identifying the factors involved in the process may lead to new therapies for various bone diseases. To clarify our understanding of the potential mechanism responsible, we compared and quantitated the extent of flew bone formation stimulated by human tumors (HeLa, Hep-2, AV-3, FL, WISH and KB), some of which have osteogenic activity in vivo [2]. Tumor cells were injected over the calvaria of nude mice to examine formation of new bone. The tumor cells produced three histologically distinct patterns of new bone growth: (1) WISH and KB stimulated appositional bone growth adjacent to periosteal bone 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 μm, and Hep-2 cells produced bone 330 μm thick. PCR and Northern blot analysis of mRNA isolated from cultured tumor cells revealed that all cell lines expressed mRNA for TGFβ, (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 serum-free conditioned media from Hep2 and HeLa cells purified by heparin affinity chromatography, we have identified FGF-1, FGF-2, and PDGF by immunodetection with specific antibodies. Our results show that new bone growth caused by these minors is likely due to the production of bone growth factors by the tumor cells, and that the overall effects on bone may be due to several factors working in concert.

Original languageEnglish (US)
Pages (from-to)210-215
Number of pages6
JournalCalcified Tissue International
Volume60
Issue number2
DOIs
StatePublished - Feb 1997

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Tumor Cell Line
Osteogenesis
Bone Development
Fibroblast Growth Factor 1
Bone and Bones
Neoplasms
Messenger RNA
Fibroblast Growth Factor 2
Cultured Tumor Cells
Minors
Cell Line
Periosteum
Bone Diseases
Serum-Free Culture Media
Conditioned Culture Medium
Insulin-Like Growth Factor I
Affinity Chromatography
HeLa Cells
Skull
Nude Mice

Keywords

  • Bone formation
  • Calvaria
  • Growth factor
  • Histomorphometry
  • Tumor

ASJC Scopus subject areas

  • Endocrinology

Cite this

Izbicka, E., Dunstan, C. R., Horn, D., Harris, M., Harris, S. E., Adams, R., & Mundy, G. R. (1997). Effects of human tumor cell lines on local new bone formation in vivo. Calcified Tissue International, 60(2), 210-215. https://doi.org/10.1007/s002239900216

Effects of human tumor cell lines on local new bone formation in vivo. / Izbicka, E.; Dunstan, C. R.; Horn, D.; Harris, M.; Harris, Stephen E; Adams, R.; Mundy, G. R.

In: Calcified Tissue International, Vol. 60, No. 2, 02.1997, p. 210-215.

Research output: Contribution to journalArticle

Izbicka, E, Dunstan, CR, Horn, D, Harris, M, Harris, SE, Adams, R & Mundy, GR 1997, 'Effects of human tumor cell lines on local new bone formation in vivo', Calcified Tissue International, vol. 60, no. 2, pp. 210-215. https://doi.org/10.1007/s002239900216
Izbicka E, Dunstan CR, Horn D, Harris M, Harris SE, Adams R et al. Effects of human tumor cell lines on local new bone formation in vivo. Calcified Tissue International. 1997 Feb;60(2):210-215. https://doi.org/10.1007/s002239900216
Izbicka, E. ; Dunstan, C. R. ; Horn, D. ; Harris, M. ; Harris, Stephen E ; Adams, R. ; Mundy, G. R. / Effects of human tumor cell lines on local new bone formation in vivo. In: Calcified Tissue International. 1997 ; Vol. 60, No. 2. pp. 210-215.
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