Overexpression of fibroblast growth factor 1 in MCF-7 breast cancer cells facilitates tumor cell dissemination but does not support the development of macrometastases in the lungs or lymph nodes.
Mice bearing primary tumors produced by LacZ-tagged MCF-7 human breast carcinoma cells transfected with fibroblast growth factor (FGF) 1 have frequent micrometastases, but macrometastases are not observed. i.v. injection of FGF-1-transfected tumor cells produced no pulmonary macrometastases, and removal of primary tumors resulted in the disappearance of spontaneous micrometastases. Thus, failure of micrometastases to proliferate was not due to inhibitory factors released from the primary tumor, and the presence of the primary tumor is required for maintenance of the micrometastases. This indicates that the micrometastases result from continued seeding from the primary tumor balanced by clearance from the metastatic site. Tumor emboli trapped in the vessels of lungs and lymph nodes and single tumor cells observed in the pulmonary vein implied that FGF-1-overexpressing MCF-7 cells are deficient in their ability to extravasate. The frequency of tumor cells incorporating bromodeoxyuridine was consistently lower in lung tissues when compared with primary tumors, indicating that disseminated tumor cells were unable to maintain a high rate of proliferation. Increased angiogenesis resulting from FGF-1 production by the transfected cells with a concomitant increased rate of intravasation into developing blood vessels may be the underlying determinant of spontaneous micrometastasis produced by these cells when compared with parental MCF-7 cells.
Zhang
L
L
Lombardi Cancer Center, Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Kharbanda
S
S
McLeskey
S W
SW
Kern
F G
FG
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology* / Q000503:physiopathology; D010052:Ovariectomy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1