Inhibition or Promotion of Tumor Growth by Granulocyte-Macrophage Colony Stimulating Factor Derived from Engineered Tumor Cells is Dose-dependent

Abstract

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. Materials and Methods: In order to determine whether there is a dose-dependent effect of GM-CSF on tumor growth, murine GMCSF-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. Conclusion: The inhibition or promotion of tumor growth by GM-CSF secreted from tumor cells is dose-dependent.