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Inhibition of FGF receptor activity in glioma implanted into the mouse brain using the tetracyclin-regulated expression system
- Source :
- Angiogenesis. 7:105-113
- Publication Year :
- 2004
- Publisher :
- Springer Science and Business Media LLC, 2004.
-
Abstract
- We have investigated growth and vascularization of malignant glioma in mice upon conditional inhibition of fibroblast growth factor (FGF) receptor activity. C6 rat glioma cells were transfected with a dominant-negative fibroblast growth factor receptor-2 (FGFR2-DN) cDNA under the control of a tetracycline-regulated expression promoter (tet off) and implanted in the brain of immunodeficient mice. Magnetic resonance imaging analysis showed a significant decrease in tumor growth 14 days after implantation when FGFR2-DN was expressed compared to control. This size difference disappeared after 20 days. However, after 20 days, tumor and endothelial cells apoptosis were higher in the FGFR2-DN group and consequently angiogenesis was decreased whereas tumor cells were similarly associated with blood vessels at the tumor periphery. Pericyte coverage was not different between the two groups but a higher amount of pericytes not associated with vessels was found in the FGFR2-DN expressing group. This demonstrates, that conditional expression of inhibitor of FGF receptor activity in gliomas implanted in the brain of immunodeficient mice can be achieved efficiently, and that FGFs are major players in glioma development and in glioma angiogenesis.
- Subjects :
- Vascular Endothelial Growth Factor A
Cancer Research
Physiology
Angiogenesis
Genetic Vectors
Clinical Biochemistry
Apoptosis
Biology
Transfection
Fibroblast growth factor
Neovascularization
Mice
Cell Line, Tumor
Glioma
medicine
Animals
Receptor, Fibroblast Growth Factor, Type 2
Receptor
Cell Proliferation
Neovascularization, Pathologic
Cell growth
Brain
Receptor Protein-Tyrosine Kinases
Tetracycline
medicine.disease
Receptors, Fibroblast Growth Factor
Rats
Gene Expression Regulation
Cell culture
Immunology
Cancer research
medicine.symptom
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 15737209 and 09696970
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Angiogenesis
- Accession number :
- edsair.doi.dedup.....75822f9b1bab005119c4b0bb535c3f91