| title: | Regulation of extracellular matrix proteins and proteases during progression of maligant gliomas: from understanding of basic mechanisms to experimental theraphy. |
|---|---|
| reg no: | ETF5446 |
| project type: | Estonian Science Foundation research grant |
| subject: |
3. Medical Sciences |
| status: | completed |
| institution: | TU Faculty of Medicine |
| head of project: | Toomas Asser |
| duration: | 01.01.2003 - 31.12.2005 |
| description: | Gliomas are the most common group of tumours of the nervous system, which are characterised by rapid growth, malignant progression and by invasion of tumour cells into the surrounding neuropil. Extracellular matrix (ECM) molecules and proteases are though tho play a key role in regulation of tumor invasion. Current project aims at detailed description of ECM molecules and proteases in the central nervous system in general and especially in glioma invasion using both functional and correlative analyses. In addition, we are willing to use a proteolysis system (uPA-uPAR system) to target and specifically eliminate invasive glioma cells in in vivo glioma animal model. Specific aims of the project are the following: 1) Expression mapping of proteases and ECM molecules in developing and adult CNS - Systematic characterization of expression patterns of proteases (MT5-MMP, MMP-28, neurosin, hippostasin) and ECM molecules on tissue microarrays of human CNS. - Expression analysis of extracellular proteases by murine neural stem cells during in vitro and in vivo migration and differentiation. 2) Analysis of expression of ECM molecules and proteases in human gliomas. - Biochemical and histological expression analysis of uPA, uPAR, tPA, neuroserpin and vitronectin in panel of human gliomas, correlation of the expression with histological malignancy grade, clinical outcome and neovascularization process. - Analysis of expression patterns of ECM proteins (fibronectin, laminin, collagen IV, tenascin and vitronectin) in biopsy specimens of human gliomas in the context of extracellular proteolysis machinery. - Analysis of serum levels of plasminogen activators, neuroserpin, uPAR and gelatinases in glioma patients as candidate prognostic factors. 3) Experimental theraphy of human malignant glioma xenografts in immunodeficient mice using uPA-dependent anthrax toxin. The results of the project are expected to be useful in practical morphological diagnostics of brain tumours, in in prognostic evaluation of glioma patients and in developing new strategies for treatment of human gliomas. In additon, these studies should give additional insight into the role of extracellular proteases in the normal developing and adult central nervous system. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Toomas Asser | TU Faculty of Medicine | Professor | |
| 2. | Andres Kulla | Deparment of Pathology of Tartu University Clinics | Director | |
| 3. | Aadu Simisker | Department of Neurology and Neurosurgery | Ph.D. student | |
| 4. | Tambet Teesalu | Department of Neurology and Neurosurgery, UT | senior research scientist | |