methylcellulose and Osteosarcoma

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.

Topics: 3T3 Cells; Animals; Blotting, Southern; Bone Neoplasms; Carcinogenicity Tests; Cell Division; Disease Models, Animal; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Methylcellulose; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Osteosarcoma; Retroviridae; Stimulation, Chemical; Tumor Cells, Cultured

Poly I:C/poly-L-lysine (poly ICL) was effective in preventing or delaying the development of osteogenic sarcoma (OGS) in mice. C57BL/6J mice were inoculated subcutaneously with 5 X 10(4) OGS cells and treatment was evaluated by palpable tumor development and subsequent day of death. A significant antitumor effect resulted from injection of 150 microgram of poly ICL into the tumor site starting immediately after tumor implant and followed by four subsequent treatments. Seventy percent of treated animals remained tumor free at 50 days, a time at which 70% of placebo treated animals had died as a result of tumor development. A similar treatment regimen of mice inoculated with 2 X 10(5) OGS cells resulted in a significant delay of time to tumor and subsequent day of death. Treatments with poly ICL were ineffective if they were initiated after development of palpable tumor or if they were administered at a nontumorous site on the animal. These findings indicate that the optimal therapy resulted from repeated intratumor treatment prior to development of extensive tumor burden.

Topics: Animals; Antineoplastic Agents; Carboxymethylcellulose Sodium; Cell Transformation, Neoplastic; Interferon Inducers; Methylcellulose; Mice; Mice, Inbred C57BL; Osteosarcoma; Peptides; Poly I-C; Polylysine; Sarcoma, Experimental; Time Factors