Projects / Programmes
Cell-biological mechanisms of the urinary bladder multifocal tumor formation
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
Bladder, cancer, urothelium, glycosaminoglycans, cell-cell junctions, cancer invasion, fluorescence microscopy, electron microscopy
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
34354 |
PhD Urška Dragin Jerman |
Oncology |
Head |
2019 - 2021 |
60 |
Organisations (1)
Abstract
Bladder cancer is one of the most common cancers worldwide. Due to the frequent occurrence of multifocal tumors, its high recurrence rate and the possibility of progression to the invasive forms of the disease, bladder cancer treatment requires long-term follow-up of patients and as such represents a major social and economic problem. The vast majority of the bladder cancer research focuses on genetic and molecular analyses of the tumors, while the mechanisms involved in dissemination of urothelial cancer cells that lead to multifocal or recurrent bladder tumors remain unidentified. Cancer urothelial cells rarely attach to the highly differentiated urothelium, whereas tumor resection and/or inflammatory reaction that result in exposed lamina propria or partially differentiated urothelial cells facilitate their implantation and formation of a novel tumor. The proposed project will aim at identification of molecules that prevent attachment of cancer urothelial cells to the highly differentiated urothelium, as well as molecules involved in attachment of cancer urothelial cells to the partially differentiated urothelium and their invasion into the urothelium. Explicitly, we will be interested in: 1) role of the glycosaminoglycan layer (GAG layer) in inhibiting the attachment of invasive cancer urothelial cells to the highly differentiated urothelium, 2) determination of the sequence of events during the attachment of the invasive cancer urothelial cells to the partially differentiated urothelium, especially in regard to the identification of cell-cell junctions between cancer and normal urothelial cells, and 3) analysis of mechanisms involved in cancer urothelial cell invasion into the partially differentiated urothelium. To accomplish these objectives, we will use urothelial in vitro models that mimic the highly differentiated or injured urothelium in vivo, on which we will seed invasive cancer urothelial cells. The study is designed as an integrated research approach composed of biochemical and advanced microscopy techniques, including fluorescence, electron microscopy and correlative light and electron microscopy. The obtained data will provide novel knowledge about the molecules and cell-biological processes involved in the dissemination of invasive cancer urothelial cells, and will as such contribute to the understanding of the multifocal bladder cancer biogenesis. Additionally, the results of this study could in the future lead to the improvement of existing and/or development of novel bladder cancer treatments, aimed at preventing the occurrence of multifocal bladder tumors and recurrence of the disease, which is extremely important for the protection of the human health.
Significance for science
Bladder cancer is one of the most common cancers worldwide with the highest incidence rates in developed countries of Europe and North America. According to the population ageing and growth, the absolute incidence of bladder cancer is expected to escalate in the future. Only in Slovenia, the incidence of bladder cancer is estimated to increase for 92 % in men and for 256 % in women by 2030 [1]. Due to the high recurrence rate, the occurrence of multifocal tumors and the possibility of progression to the life threatening invasive forms of the disease, the bladder cancer treatment requires long-term follow-up of patients and represents a major social and economic problem. In bladder cancer research there is a clear lack of studies that would explain the mechanisms involved in dissemination of urothelial cancer cells that lead to multifocal or recurrent bladder tumors. The genetic studies of the multifocal bladder cancer support the assumption that cancer urothelial cells spread by release of cancer urothelial cells from the primary tumor and by their implantation into the normal urothelium at a distant site. The cell-biological mechanisms involved in this phenomenon, understanding of which is crucial for development of effective prevention strategies of multifocal bladder tumor occurrence and their recurrence, are not yet investigated or understood and are the main subject of the proposed project. The obtained data will provide a novel knowledge that will contribute to the understanding of the still unresolved questions regarding the mechanisms of spread, i.e. attachment and invasion, of cancer urothelial cells, which is relevant and of great significance for the understanding of the cancer cell dissemination biology, not only in bladder cancer, but also in cancer generally.
The research group of Institute of Cell Biology successfully collaborates with the urologists of the University Medical Centre Ljubljana. The ambition of the proposed project will be thus also to develop conception of the multidisciplinary approaches that will in the future enable translation of the high-quality knowledge acquired in basic research into the clinical practice. In accordance, the results obtained from this study could in the future lead to the improvement of existing and development of new bladder cancer treatments, aimed at preventing the occurrence of multifocal bladder tumors and recurrence of the disease, which is extremely important for the protection of human health. Nevertheless, at present, the designed in vitro models could be used as research tools for preclinical studies aimed at the development and testing of potential new anti-bladder cancer drugs.
References
1. Wong, M.C.S., et al., The global epidemiology of bladder cancer: a joinpoint regression analysis of its incidence and mortality trends and projection. Sci Rep, 2018. 8(1): p. 1129.
Significance for the country
Bladder cancer is one of the most common cancers worldwide with the highest incidence rates in developed countries of Europe and North America. According to the population ageing and growth, the absolute incidence of bladder cancer is expected to escalate in the future. Only in Slovenia, the incidence of bladder cancer is estimated to increase for 92 % in men and for 256 % in women by 2030 [1]. Due to the high recurrence rate, the occurrence of multifocal tumors and the possibility of progression to the life threatening invasive forms of the disease, the bladder cancer treatment requires long-term follow-up of patients and represents a major social and economic problem. In bladder cancer research there is a clear lack of studies that would explain the mechanisms involved in dissemination of urothelial cancer cells that lead to multifocal or recurrent bladder tumors. The genetic studies of the multifocal bladder cancer support the assumption that cancer urothelial cells spread by release of cancer urothelial cells from the primary tumor and by their implantation into the normal urothelium at a distant site. The cell-biological mechanisms involved in this phenomenon, understanding of which is crucial for development of effective prevention strategies of multifocal bladder tumor occurrence and their recurrence, are not yet investigated or understood and are the main subject of the proposed project. The obtained data will provide a novel knowledge that will contribute to the understanding of the still unresolved questions regarding the mechanisms of spread, i.e. attachment and invasion, of cancer urothelial cells, which is relevant and of great significance for the understanding of the cancer cell dissemination biology, not only in bladder cancer, but also in cancer generally.
The research group of Institute of Cell Biology successfully collaborates with the urologists of the University Medical Centre Ljubljana. The ambition of the proposed project will be thus also to develop conception of the multidisciplinary approaches that will in the future enable translation of the high-quality knowledge acquired in basic research into the clinical practice. In accordance, the results obtained from this study could in the future lead to the improvement of existing and development of new bladder cancer treatments, aimed at preventing the occurrence of multifocal bladder tumors and recurrence of the disease, which is extremely important for the protection of human health. Nevertheless, at present, the designed in vitro models could be used as research tools for preclinical studies aimed at the development and testing of potential new anti-bladder cancer drugs.
References
1. Wong, M.C.S., et al., The global epidemiology of bladder cancer: a joinpoint regression analysis of its incidence and mortality trends and projection. Sci Rep, 2018. 8(1): p. 1129.
