Inhibition or promotion of tumor growth by granulocyte-macrophage colony stimulating factor derived from engineered tumor cells is dose-dependent.
BACKGROUND
Granulocyte-macrophage colony stimulating factor (GM-CSF) has been widely investigated as an adjuvant factor for tumor immunotherapy. However, the results are controversial with antitumor effects in some studies and a tumor growth promotion effect in others.


METHODS
In order to determine whether there is a dose-dependent effect of GM-CSF on tumor growth, murine GM-CSF-expressing vector was constructed and transfected into TC-1 tumor cells and various clones stably expressing different levels of GM-CSF were obtained. The growth of these clones in vivo was studied.


RESULTS
Although these clones grow at a similar rate in vitro, their growth in vivo is dramatically different. Clones expressing high levels (>10,000 pg/ml) of GM-CSF grow significantly faster than the control (p <0.001); clones expressing low levels (<100 pg/ml) of GM-CSF grow significantly slower than the control (p<0.001); while clones expressing intermediate levels (1000-2000 pg/ml) of GM-SCF grow at a similar rate as the control (p >0. 05). The high levels of GM-CSF secreted by tumor cells induced granulocytosis and lymphopenia. The antitumor growth effect induced by low levels of GM-CSF is not due to the function of lymphocytes.


CONCLUSIONS
The inhibition or promotion of tumor growth by GM-CSF secreted from tumor cells is dose-dependent.
Li
Jinhua
J
Oncology Research Institute, Greenville Hospital System, Greenville, SC 29605, USA.
Bouton-Verville
Hilary
H
Holmes
Lillia M
LM
Burgin
Kelly E
KE
Jakubchak
Susan
S
Yu
Xianzhong
X
Wagner
Thomas E
TE
Wei
Yanzhang
Y
D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D002999:Clone Cells; D005260:Female; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
D016178:Granulocyte-Macrophage Colony-Stimulating Factor