The effect of GM-CSF and G-CSF on the growth of human osteosarcoma cells in vitro and in vivo

Int J Cancer. 1994 Jan 15;56(2):236-43. doi: 10.1002/ijc.2910560216.

Abstract

The human osteosarcoma cell line, MG63, responds both to GM-CSF and to G-CSF in vitro. To assess the significance of these observations to tumor growth in vivo, MG63 cells were engineered by retroviral infection to produce human GM-CSF or G-CSF. These retrovirally infected cells become autostimulatory as measured by increased [3H]-thymidine incorporation (3- to 7-fold) and anchorage-independent colony formation (7- to 10-fold) as compared with uninfected MG63 cells or cells infected with control (neor) retrovirus. The increased proliferation induced by exogenous GM-CSF or G-CSF on uninfected MG63 cells in both assays could be completely inhibited by anti-GM-CSF or anti-G-CSF antibodies, while the same antibodies only partially abrogated proliferation by the growth-factor-producing cells. None of 34 nude or SCID mice developed tumors when injected s.c. with uninfected or neor-virus-infected cells. In contrast, all 30 mice injected with GM-CSF- or G-CSF-producing MG63 cells developed tumors which were G418-resistant and factor-producing. Tumor cell DNA showed a polyclonal retroviral integration pattern indistinguishable from that in the DNA of cells injected into mice. Tumors that formed following injection of a mixture of G418-resistant, GM-CSF-producing cells and cells infected with virus containing only the hygror gene contained hygromycin-resistant cells in the same proportion as was present in the original cell mixture. These data indicate that GM-CSF and G-CSF can support the growth of an osteosarcoma cell line both in vitro and in vivo whether the factor is supplied by autocrine production or from exogenous sources.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / microbiology
  • Animals
  • Blotting, Southern
  • Bone Neoplasms / immunology
  • Bone Neoplasms / microbiology
  • Bone Neoplasms / pathology*
  • Carcinogenicity Tests
  • Cell Division / drug effects
  • Disease Models, Animal
  • Female
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Male
  • Methylcellulose / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mice, SCID
  • Osteosarcoma / immunology
  • Osteosarcoma / microbiology
  • Osteosarcoma / pathology*
  • Retroviridae / genetics
  • Retroviridae / metabolism
  • Retroviridae / physiology
  • Stimulation, Chemical
  • Tumor Cells, Cultured / drug effects

Substances

  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Methylcellulose