Overexpression of VEGF121, but not VEGF165 or FGF-1, improves oxygenation in MCF-7 breast tumours.
Vascular endothelial growth factor (VEGF) is an intensively studied molecule that has significant potential, both in stimulating angiogenesis and as a target for antiangiogenic approaches. We utilised MCF-7 breast cancer cells transfected with either of two of the major VEGF isoforms, VEGF(121) or VEGF(165), or fibroblast growth factor-1 (FGF-1) to distinguish the effects of these factors on tumour growth, vascular function, and oxygen delivery. While each transfectant demonstrated substantially increased tumorigenicity and growth rate compared to vector controls, only VEGF(121) produced a combination of significantly reduced total and perfused vessel spacing, as well as a corresponding reduction in overall tumour hypoxia. Such pathophysiological effects are of potential importance, since antiangiogenic agents designed to block VEGF isoforms could in turn result in the development of therapeutically unfavourable environments. If antiangiogenic agents are also combined with conventional therapies such as irradiation or chemotherapy, microregional deficiencies in oxygenation could play a key role in ultimate therapeutic success.
Fenton
B M
BM
Department of Radiation Oncology, University of Rochester Medical Center, Box 704, Rochester, NY 14642, USA. bruce.fenton@rochester.edu
Paoni
S F
SF
Liu
W
W
Cheng
S-Y
SY
Hu
B
B
Ding
I
I
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016220:Fibroblast Growth Factor 1; D010100:Oxygen