A correlation between GM-CSF gene expression and metastases in murine tumors.
Using 14 transplantable murine tumors, we investigated a possible correlation between their ability to produce the cytokine GM-CSF and the spontaneous metastatic potential when mice were subcutaneously inoculated. The following results were obtained: (1) seven tumors, which produced severe pulmonary metastases and metastatic swelling of lymph nodes, exhibited the ability to produce GM-CSF activity in culture. The cell population analysis revealed that the cells producing GM-CSF were tumor cells themselves, but that contaminating macrophages/granulocytes and T lymphocytes did not produce GM-CSF. The mRNA for GM-CSF was also found in all of these highly metastatic tumors tested. In mice inoculated with a highly metastatic tumor, the GM-CSF mRNA was also found in lungs; (2) in 3 other tumors, which produced histological but not macroscopical pulmonary metastases, no GM-CSF activity could be detected in the culture fluids. GM-CSF mRNA was, however, detected in the tumor cells in the presence of an mRNA-stabilizing agent, cycloheximide, suggesting the possibility that the tumor cells of this type were transcribing GM-CSF gene, and secreting it in undetectable levels; (3) in culture of the 4 remaining poorly or non-metastatic tumors, neither CSF activity nor GM-CSF mRNA could be detected even in the presence of cycloheximide. GM-CSF mRNA was also not found in lungs of tumor-bearing mice. Our results indicate that there may be a correlation between GM-CSF gene expression in tumor cells and spontaneous metastases.
Takeda
K
K
Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan.
Hatakeyama
K
K
Tsuchiya
Y
Y
Rikiishi
H
H
Kumagai
K
K
D000818:Animals; D003115:Colony-Stimulating Factors / Q000378:metabolism; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics*; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor