Projects / Programmes
Role of cysteine cathepsins in complement activation in cancer
| Code |
Science |
Field |
Subfield |
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 1.06 |
Natural Sciences |
Biological sciences |
Proteases, cysteine cathepsins, cancer, complement, C1q, inflammation-associated diseases
Researchers (7)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
39130 |
PhD Monika Biasizzo |
Biochemistry and molecular biology |
Researcher |
2021 - 2023 |
28 |
| 2. |
33315 |
PhD Miha Butinar |
Biology |
Researcher |
2019 |
60 |
| 3. |
18801 |
PhD Marko Fonović |
Biochemistry and molecular biology |
Researcher |
2019 - 2023 |
187 |
| 4. |
37797 |
PhD Georgy Mikhaylov |
Biochemistry and molecular biology |
Researcher |
2019 - 2023 |
54 |
| 5. |
07561 |
PhD Boris Turk |
Biochemistry and molecular biology |
Head |
2019 - 2023 |
1,037 |
| 6. |
50513 |
Eva Vidak |
Biochemistry and molecular biology |
Junior researcher |
2019 - 2022 |
15 |
| 7. |
33762 |
PhD Robert Vidmar |
Biochemistry and molecular biology |
Researcher |
2019 - 2023 |
148 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0106 |
Jožef Stefan Institute |
Ljubljana |
5051606000 |
90,695 |
Abstract
Innate immune response plays a crucial role in antitumour defense. One of the key elements is the complement system, although recent evidence suggests that activation of complement can be subverted in tumour microenvironment to promote tumor growth and metastasis spread. Another factor, which is subverted in tumor microenvironment to contribute to tumor development are cysteine cathepsins, a group of proteases normally confined to the endolysosomal system. In cancer, they are secreted into the extracellular milieu, where they degrade the components of the extracellular matrix, activate or inactivate cytokines and chemokines, as well as shed membrane-anchored adhesion proteins and receptors. There is scarce evidence that they may be linked also to regulation of complement, but the mechanisms are not clear. However, our preliminary in vitro evidence suggests that cathepsins L and S can almost completely blunt complement activation upstream of C3 activation on cancer cells.
The main goal of the project is therefore to unravel the molecular mechanisms behind the cathepsin-mediated regulation of the complement system in cancer, combining biochemical, proteomic and molecular and cell biology approaches with in vivo analysis in mouse cancer models. We believe that the results will reveal novel roles of individual cathepsins in the regulation of the complement system in cancer, thereby also opening new strategies for anti-cancer therapies. Moreover, this would allow transfer to other inflammation-associated diseases with the involvement of cathepsins and complement.
Significance for science
There is still a significant unmet need for successful early diagnosis and treatment of major life-threatening or debilitating diseases like cancer and other inflammation-associated diseases, making this project of high biomedical relevance. One of the major reasons is that these diseases are still not well understood at the molecular level. The same is true also for the role of cysteine cathepsins and complement in these diseases. Using a combination of biochemical, proteomic and in vivo experiments, important new information will be obtained that will shed light on cancer progression and on the role of cysteine cathepsins in these diseases, including in complement regulation. Moreover, the project is expected to open new avenues in the area of of complement research, which recently began to emerge as one of the key factors in development of tumorigenesis. Identification of C1q ligands on the surface of cancer cells would be the real highlight of the project and a major breakthrough in all these areas of research, including complement, cancer and proteolysis. The gained knowledge will thus not only significantly contribute to our understanding of the complex biological phenomena, but will also be instrumental in biomedical research to understand and develop novel strategies to combat cancer and other inflammation-associated diseases.
Significance for the country
There is still a significant unmet need for successful early diagnosis and treatment of major life-threatening or debilitating diseases like cancer and other inflammation-associated diseases, making this project of high biomedical relevance. One of the major reasons is that these diseases are still not well understood at the molecular level. The same is true also for the role of cysteine cathepsins and complement in these diseases. Using a combination of biochemical, proteomic and in vivo experiments, important new information will be obtained that will shed light on cancer progression and on the role of cysteine cathepsins in these diseases, including in complement regulation. Moreover, the project is expected to open new avenues in the area of of complement research, which recently began to emerge as one of the key factors in development of tumorigenesis. Identification of C1q ligands on the surface of cancer cells would be the real highlight of the project and a major breakthrough in all these areas of research, including complement, cancer and proteolysis. The gained knowledge will thus not only significantly contribute to our understanding of the complex biological phenomena, but will also be instrumental in biomedical research to understand and develop novel strategies to combat cancer and other inflammation-associated diseases.
