Macrophage colony-stimulating factor (CSF-1) enhances invasiveness in CSF-1 receptor-positive carcinoma cell lines.
We have identified two lung carcinoma cell lines, A549 and Calu-1, expressing low levels of the macrophage colony-stimulating factor (CSF-1) receptor (CSF-1R), encoded by the c-fms oncogene. The effect of CSF-1 on the invasive potential of these CSF-1R-positive tumor cell lines and on two other CSF-1R-bearing cell lines, the BT-20 breast carcinoma cell line and the CSF-1 growth-dependent murine macrophage cell line BAC1.2F5, was examined using a human amnionic basement membrane invasion model. Culture of A549, Calu-1, and BAC1.2F5 cells with CSF-1 (250 ng/ml) resulted in a maximal 12-, 5-, and 12-fold enhancement of invasion, respectively, compared to control cells cultured in medium alone. Larger concentrations of CSF-1 (750 ng/ml) reduced A549 and Calu-1 invasiveness compared to the effect of the 250-ng/ml dose. Maximal enhancement in invasion of A549 and Calu-1 cells occurred after a 24- and 48-h exposure to CSF-1, respectively. CSF-1 increased invasiveness 6-fold in BT-20 cells induced by glucocorticoids to express high levels of CSF-1R, in comparison to control cells not exposed to glucocorticoids or CSF-1. In contrast, CSF-1 had no effect on invasion in the CSF-1R-negative MCF-7 cell line. Culture of A549 and Calu-1 cells with other cytokines and growth factors including GM-CSF (500 units/ml), IL-3 (1 ng/ml), interferon-gamma (500 units/ml), and tumor necrosis factor (50 units/ml) had no significant effect on invasiveness. Thus, CSF-1 increases invasiveness in CSF-1R-positive tumor cell lines, suggesting a role in enhancing the metastatic potential of tumor cells expressing the CSF-1R.
Filderman
A E
AE
Pulmonary and Critical Care Section, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Bruckner
A
A
Kacinski
B M
BM
Deng
N
N
Remold
H G
HG
D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis* / Q000235:genetics
D016207:Cytokines; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor