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The effect of GM‐CSF and G‐CSF on the growth of human osteosarcoma cells in vitro and in vivo
Author(s) -
Thacker J. Dean,
Dedhar Shoukat,
Hogge Donna E.
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910560216
Subject(s) - osteosarcoma , in vivo , biology , in vitro , cell culture , microbiology and biotechnology , antibody , growth factor , retrovirus , cell growth , polyclonal antibodies , virus , cancer research , virology , immunology , biochemistry , genetics , receptor
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 [ 3 H]‐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 (neo r ) 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 neo r ‐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 hygro r 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.