Loss of tumorigenicity of human breast cancer cells engineered to produce IL-2, IL-4 or GM-CSF in nude mice.
Human breast cancer cells (OCUB-M), retrovirally transduced with granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-2 (IL-2) or IL-4 gene were examined for their antitumor activities in nude mice. Although cell proliferation rates in vitro of these cytokine-producing cells were not significantly different from that of wild-type cells, nude mice that were subcutaneously inoculated with cytokine-producing cells did not develop tumors in contrast to mice that were injected with wild-type cells. Injection of GM-CSF-producing cells into the vicinity of growing wild-type tumors retarded subsequent growth of wild-type tumors. Histological examination of tumors which received GM-CSF-producing cells revealed marked infiltration of mononuclear cells around the tumors. Irradiation of cytokine-producing cells diminished their proliferation capacity but production of cytokine(s) was retained. Therefore, inoculation of irradiated cytokine producer cells into growing tumors can be used as a therapeutic maneuver for breast cancer.
Maeda
T
T
Department of Surgery (II), School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Matsubara
H
H
Sugaya
M
M
Miyazawa
Y
Y
Gunji
Y
Y
Ochiai
T
T
Sakiyama
S
S
Tagawa
M
M
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D002455:Cell Division; D002470:Cell Survival / Q000528:radiation effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor