Role of tumor-derived granulocyte-macrophage colony-stimulating factor in mice bearing a highly invasive and metastatic mammary carcinoma.
We have examined the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in tumor-bearing BALB/c mice using the syngeneic F3II mammary carcinoma. In the present model, progression of subcutaneous tumors induced massive myelopoiesis in bone marrow and spleen due to GM-CSF secretion by tumor cells. In vitro, the addition of recombinant mouse GM-CSF (5- 25 ng/ml) caused a significant increase in F3II cell growth, either in the presence or absence of serum. Zymographic analysis of conditioned media from F3II monolayers showed that GM-CSF exerted a dose-dependent enhancement in the metalloproteinases MMP-9 (105 kD) and MMP-2 (70 kD), key enzymes in mammary tumor cell invasion. Our data suggest that ectopic GM-CSF production stimulates myelopoiesis and may also play an important role in tumor progression and metastasis formation.
Gabri
M R
MR
Laboratory of Molecular Oncology, Department of Science and Technology, Quilmes National University, Bernal, Argentina.
Menna
P L
PL
Scursoni
A M
AM
Gomez
D E
DE
Alonso
D F
DF
D000818:Animals; D014408:Biomarkers, Tumor; D001853:Bone Marrow / Q000378:metabolism*; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology*; D019891:Leukopoiesis / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D013154:Spleen / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9