رسالة جامعية
The influence of neuronal calcium sensor 1 on metastasis of triple-negative breast cancer
| العنوان: | The influence of neuronal calcium sensor 1 on metastasis of triple-negative breast cancer |
|---|---|
| المؤلفون: | Apasu, Jonathan Edem |
| المساهمون: | Jabs, Ronald, Baader, Stephan |
| بيانات النشر: | Universitäts- und Landesbibliothek Bonn |
| سنة النشر: | 2020 |
| المجموعة: | bonndoc - The Repository of the University of Bonn |
| مصطلحات موضوعية: | Brustkrebs, Metastasierung, Lungenmetastasierung, prognostischer Marker, therapeutischer Marker, Mausmodell, Zellmigration, zelluläres Überleben, Kalzium-bindende Proteine, cell migration, breast cancer, metastasis, lung metastasis, prognostic marker, therapeutic marker, mouse model, cell survival, calcium binding protein, ddc:610 |
| الوصف: | At present, breast cancer is the leading global cause of cancer morbidity and mortality in women. The most aggressive subtype - triple-negative breast cancer - evades current targeted therapy schemes and lacks sufficient prognostic markers to predict disease progression. Hence, there is an urgent clinical need for novel prognostic and therapeutic biomarkers. High expression of NCS1 has been linked to poor outcomes in breast cancer patients as well as in patients suffering from liver cancer. Recent investigations suggest that high NCS1 levels accelerate metastatic spread of breast cancer by promoting crucial pro-metastatic capabilities. Moreover, previous in vitro studies provide strong evidence of increased cancer cell invasion, increased cancer cell survival and altered cancer cell adhesion due to high NCS1 levels. To test if these metastasis enhancing phenotypes also confer a functional effect in vivo, the effect of increased NCS1 on the metastatic capabilities of triple-negative breast cancer cells were investigated in a mouse xenograft model. By utilizing a luciferase, photon-flux based, life imaging system, significantly accelerated lung metastasis formation by NCS1 overexpressing breast cancer cells, as compared to cells with a control level of NCS1, was demonstrated. Histopathological assessment of the developed lung metastases further delivered profound evidence that NCS1 overexpression facilitated early metastatic spread to the lungs and additionally increased cancer cell survival in mature metastases by preventing necrosis. In an attempt to elucidate the metastasis promoting mechanisms, in vitro experiments were conducted. Herein, a migration favoring cellular phenotype of NCS1 overexpressing cells, as well as close association of NCS1 with actin in cellular protrusions, were successfully demonstrated. The observation of increased cell motility of NCS1 overexpressing cells in 2-D and 3-D motility assays confirmed a functional effect of this phenotype. NCS1, as a calcium binding protein, plays a crucial ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:5-59858; https://hdl.handle.net/20.500.11811/8666Test |
| الإتاحة: | https://doi.org/20.500.11811/8666Test https://doi.org/10.1096/fj.201802004RTest https://hdl.handle.net/20.500.11811/8666Test |
| حقوق: | In Copyright ; http://rightsstatements.org/vocab/InC/1.0Test/ ; openAccess |
| رقم الانضمام: | edsbas.27650AE3 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |