Projects / Programmes
The Role of Proteolytic Enzymes in Benign and Malignant Brain Tumours
| Code |
Science |
Field |
Subfield |
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| Code |
Science |
Field |
| P004 |
Natural sciences and mathematics |
Biochemistry, Metabolism |
| P320 |
Natural sciences and mathematics |
Nucleic acids, protein synthesis |
Proteolytic enzymes, proteinase inhibitors , cathepsins, cystatins; // lysosomes; // invasion, apoptosis, angiogenesis; // brain tumours, glioma, meningioma;
Researchers (6)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
18325 |
PhD Simon Caserman |
Biochemistry and molecular biology |
Researcher |
2004 |
0 |
| 2. |
07802 |
PhD Tamara Lah Turnšek |
Biology |
Head |
2004 - 2007 |
0 |
| 3. |
07736 |
PhD Bojan Sedmak |
Biochemistry and molecular biology |
Researcher |
2004 - 2005 |
0 |
| 4. |
16193 |
Nataša Sever |
Pharmacy |
Researcher |
2004 - 2007 |
0 |
| 5. |
20766 |
PhD Miha Trinkaus |
Neurobiology |
Researcher |
2004 |
0 |
| 6. |
10974 |
PhD Irena Zajc |
Biochemistry and molecular biology |
Researcher |
2004 - 2007 |
0 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0105 |
National Institute of Biology |
Ljubljana |
5055784 |
0 |
Abstract
Among lysosomal enzymes, cysteine cathepsins (CC) are the most abundant. Cathepsins B and L along with their endogenous, intracellular inhibitors, stefins A and B, are associated with cancer progression, including brain tumours (Lah et al., 2002). The ability of tumour cells (TC) to invade the surrounding tissue is characteristics of tumour malignancy and depends on the cascade of proteolytic events, which include among others matrix metalloproteinases (MMPs) and cathepsins, resulting in the degradation of extracellular matrix (ECM). Along with altered adhesion, this enables cells to migrate to distant sites in the organism. Angiogenesis is also an early marker of malignant tumours, associated with increased proliferation and invasiveness of vascular endothelial cells (EC).
The aims of this study are to investigate the association of CC with brain tumour malignancy and define the role of these cathepsins in progression of the disease, this includes:
I. Clinical studies of low invasive meningioma and high invasive glioma;
Although we demonstrated that elevated cathepsin B levels were indicative of more aggressive meningiomas, we need to confirm this in larger population of meningioma, and measure cathepsin L to relate it to cathepsin B. Cathepsin L is regulated independently of cathepsins B, has different characteristics and its role in invasion is less clear. Similarly, for comparison with cathepsin B, we have to measure cathepsin L in glioma samples.
II. Tissue culture studies on glioma and vascular EC;
a) The effects of genetic manipulation of CC and inhibition of CC and MMP by added inhibitors on invasion of brain TC in vitro; We hypothesize that simultaneous inhibition of various proteinases would synergistically effect the inhibition of invasion
b) The effects of silencing and inhibition of CC on the expression of MMP (MMP2, MMP9 and MT1-MMP) after the invasion of transfected cells in the matrix n vitro. We hypothesize the induction of MMPs, after reducing the efficacy of CC in the invasive cell phenotype.
c) The effects of synthetic and natural proteinase inhibitors on EC proliferation and invasion. We envision determining effective combination of the inhibitors for reducing angiogenesis in ex vivo rat aorta ring mode.
The result of the study will contribute to understanding the regulation of proteinases in malignant TC and EC in brain tumours and to a more informed design of proteinase inhibitors with possible synergistic effects, as potential adjuvant therapeutics.
