Fibroblast growth factors (FGFS) increase breast tumor growth rate, metastases, blood flow, and oxygenation without significant change in vascular density.
Breast tumors expressing no detectable FGFs (MCF-7) were compared with tumors transfected with FGF4 or FGF1 (FGF4/MCF-7 or FGF1/MCF-7), and with MDA-MB-435, which produce endogenous FGF2. Tumor blood flow was measured by 133Xe diffusion, oxygen distribution was measured by Eppendorf pO2 histography, and vascular density was measured by CD31 staining. Tumors that overexpress angiogenic factors grew at a rate far exceeding that of MCF-7. The FGF producing tumors also had much higher metastatic rates to lung. Tumor blood flow was significantly higher in the two FGF-transfected xenografts compared with the parent MCF7. Median tumor pO2 was also higher, and tumor oxygenation was preserved even for large tumors. The vascular density as determined by CD31 staining, however, was not markedly increased in tumors overexpressing angiogenic factors. We found that angiogenic factors preserve and augment neovascular function, thus facilitating tumor growth and progression.
Okunieff
Paul
P
Department of Radiation Oncology, University of Rochester, Rochester, NY, USA.
Fenton
Bruce M
BM
Zhang
Lurong
L
Kern
Francis G
FG
Wu
Timothy
T
Greg
J Robert
JR
Ding
Ivan
I
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010100:Oxygen / Q000378:metabolism*; D012039:Regional Blood Flow
D005346:Fibroblast Growth Factors; D010100:Oxygen