Bone metastasis

Osseous metastases are often incurable and are associated with fractures, disabilities, pain, reduced quality of life and a poor prognosis. Once metastases have formed, patients can usually only be treated with palliative cystectomy or palliative chemotherapy.
Conventional therapies have limited success in preventing or treating bone metastases, in part due to the complex nature of the bone microenvironment, tumor heterogeneity and the development of tumor cell resistance.
Until recently, the persistence of dormant tumor cells in secondary sites and their resistance to chemotherapeutic agents that preferentially target proliferating cells was not recognized as a therapeutic target.
There is a great need to identify new therapeutic strategies to prevent the colonization and growth of metastases.
Bone is a pre-metastatic niche (PMN) that supports the colonization, survival and colonization of metastatic tumor cells. In addition, bone is a homeostatic tissue that is subject to constant remodeling and degradation processes. These remodeling processes also result in the release of cytokines and growth factors such as RANK-L, IGFs, calcium and TGF-β.
These factors are significantly involved in the proliferation, migration and metastasis and in the malignant interaction (“vicious circle”) of tumor and bone cells.

Research question:
Overall, there is great interest in finding out to what extent the bone microenvironment influences the homing, proliferation, migration and colonization of tumour cells, as well as the development of resistance. A better understanding of these processes could provide clues to new therapeutic options that could prevent metastasis in the bone in the future.
Urothelial carcinoma cell lines will also be used to answer these questions. This is because, in addition to breast and prostate cancer, muscle-invasive urothelial cell carcinoma also metastasizes preferentially in the bone. It is the second most common tumor entity of the urogenital tract and the seventh most common entity in men worldwide. With a 5-year survival rate of less than 50 %, new treatment options are urgently needed here too, particularly because cisplatin-based chemotherapy has not improved significantly in the last 30 years. Chemoresistance mediation also plays an important role in UC and is one of the central complications of everyday clinical practice.

The aim of this project is to evaluate the extent to which primary human osteoblasts from elderly patients modulate metastasis-relevant parameters.

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