Loading...
Please wait, while we are loading the content...
Similar Documents
Die Rolle der residenten monozytären Zellen sowie Tumorzell-spezifischer Faktoren bei der Metastasierung des Mammakarzinoms
| Content Provider | Semantic Scholar |
|---|---|
| Author | Rietkötter, Eva |
| Copyright Year | 2013 |
| Abstract | Metastasis is the leading cause of cancer death and marks the turning point of cancer diseases where cure is rarely possible. Searching for new therapy approaches to prevent metastasis, an important finding was the identification of immune cells to support not only the first steps of tumor progression but also the process of metastasis. In this context, especially macrophages were discovered as mediators of migration and invasion of cancer cells as well as their colonization in a distant organ. Bisphosphonates (BPs) are known to be potent inhibitors of macrophages. Nevertheless, most of the current studies explain their anti-tumor activity with direct effects on the migration and invasion capacity of cancer cells but do not consider their effects on the tumor stroma. In this study we show that macrophages are much more sensitive to the nitrogen-containing BP zoledronic acid (ZA) than breast cancer cells. Furthermore, macrophage-induced invasion of MCF-7 as well as microglia-assisted colonization of brain tissue is reduced by ZA treatment while the migration and invasion capacity of the cancer cells is not affected. For a second macrophage inhibitor, a CSF-1 antibody (5A1), we show that it induces the depletion of bone marrow-derived macrophages (BMDMs) whereas it is not affecting microglia viability. While 5A1 slightly reduces microglia-induced invasion of MCF-7, it strongly inhibits BMDM-induced invasion. Not only benign cells of the tumor stroma but also cancer cell determinants can give rise to metastases. Recently, the transcription factor LEF1 could be identified to induce cerebral metastasis of lung adenocarcinomas. In this study we show that LEF1 expression can be detected in a subgroup of breast cancer brain metastases and that it is limited to invasive breast cancer cell lines. While overexpression of LEF1 in the weakly invasive MCF-7 does not affect proliferation, migration or the sensitivity towards chemotherapy or radiation, it increases the invasiveness and induces angiogenesis in the tumor. These effects are independent of the binding of the transcription factor to the DNA and seem to be mediated by a β-catenin-independent mechanism. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://ediss.uni-goettingen.de/bitstream/handle/11858/00-1735-0000-0001-BB56-3/Dissertation_Eva%20Rietk%C3%B6tter.pdf?sequence=1 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
