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Project

Cell-biological mechanisms of the urinary bladder multifocal tumor formation (postdoctoral research project)

Funder: Slovenian Research Agency

Funding period
0
Funding amount
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.
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System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Biotechnology

  • RCDC

    Cancer

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science