A correlation between GM‐CSF gene expression and metastases in murine tumors

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Abstract
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.