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Expression of the proteolytic factors, tPA and uPA, PAI-1 and VEGF during malignant glioma progression
- Source :
- International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 17(5-6)
- Publication Year :
- 1999
-
Abstract
- Various proteases and their inhibitors have been shown to be important in tumor invasion. Angiogenesis is further a prerequisite for the growth and progression of solid tumors. Since these systems are functionally linked, in situ hybridization and in situ zymography were used to investigate the spatial and temporal expression of factors representative of the plasmin/plasminogen system and of an angiogenic factor in the BT4C glioma model. This tumor is invasive with a high grade of neovascularization. Tissue-type plasminogen activator urokinase-type plasminogen activator and plasminogen activator inhibitor-1 mRNA were expressed in glioma cells during the entire tumor growth. Early in the tumor development the expression was found throughout the small tumor (approximately 10 mm3) while later in the time course the expression was found predominantly in the invasive tumor border of the tumor. The in situ zymography demonstrated that the plasminogen activators were translated into functional proteins. Vascular endothelial growth factor mRNA was expressed following a similar spatial and temporal pattern with an early expression in the entire small tumor while later, in larger tumors, it was exclusively expressed in the invasive tumor edge. In normal brain, the ventricular ependyma, meninges, as well as scattered neurons expressed tissue-type plasminogen activator mRNA. Vascular endothelial growth factor mRNA was observed in the choroid plexus, and in scattered cells in normal brain tissue. Our finding may suggest a functional co-operation of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1 and vascular endothelial growth factor during glioma progression. This model could be of value when evaluating different treatment modalities aimed at blocking the migrating capacity and growth of glial tumors.
- Subjects :
- Vascular Endothelial Growth Factor A
Angiogenesis
VEGF receptors
Endothelial Growth Factors
Neovascularization
Developmental Neuroscience
Glioma
Plasminogen Activator Inhibitor 1
medicine
Animals
neoplasms
Regulation of gene expression
Lymphokines
integumentary system
biology
Neovascularization, Pathologic
business.industry
Vascular Endothelial Growth Factors
medicine.disease
Urokinase-Type Plasminogen Activator
nervous system diseases
Neoplasm Proteins
Rats
Gene Expression Regulation, Neoplastic
Vascular endothelial growth factor A
Tissue Plasminogen Activator
Upa pai 1
Cancer research
biology.protein
medicine.symptom
business
Developmental Biology
Subjects
Details
- ISSN :
- 07365748
- Volume :
- 17
- Issue :
- 5-6
- Database :
- OpenAIRE
- Journal :
- International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
- Accession number :
- edsair.doi.dedup.....3cd3ff7cebc022cc24e82eb17212b6cd