Die Rolle von Metadherin bei der Metastasierung des Ovarialkarzinoms : = The role of Metadherin in ovarian cancer metastasis

Hochschulschrift

Zusammenfassung: This thesis investigates the contribution of the protein metadherin (MTDH) to the development and progression of metastatic ovarian cancer. Since the dismal prognosis of advanced stage ovarian cancer has changed little over the past 50 years novel molecular targets for chemotherapeutic treatment are needed and MTDH might be a promising candidate. Other groups had shown that MTDH contributes to the progression and development of various cancer entities, particularly it was demonstrated that MTDH expression inversely correlates with the overall survival of ovarian cancer patients.In this thesis an in vivo model for advanced stage ovarian cancer was established and it could be shown that the downregulation of MTDH in Mouse Ovarian Surface Epithelial cells (MOSEC) reduced the amount of distant metastases and local progression and improved survival of tumor bearing mice significantly. In vitro, our MTDH knockdown did not reduce the proliferation, migration or stem cell properties of MOSEC. We concluded that the strong in vivo effects require complex cellular interactions which were not reflected in vitro.We identified a novel MTDH exon 11 skipping variant in MOSEC which could not be found in non-malignant ovarian epithelial cells. Overexpressing the skipping variant in MOSEC, human ovarian cancer cells and human ovarian epithelial cells significantly reduced the survival of mice injected intraperitoneally with the respective cells in vivo. Wildtype MTDH and the MTDH skipping variant were exclusively localized within the cytoplasm showing no differences in intracellular distribution. Importantly, protein interaction studies indicated that the skipping variant has a stronger association to several ribosomal and RNA-binding proteins which could explain its pro-malignant effects. The MTDH exon 11 skipping variant was also found in human ovarian cancer tissues.Overall this work underlines a causal relationship between MTDH expression and the progression of ovarian cancer and indicates that a pro-malignant MTDH skipping variant exists

Object Details

• Alternative title: The role of Metadherin in ovarian cancer metastasis
• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Albert-Ludwigs-Universität Freiburg, Dissertation, 2015

Classification and Topics

• Keyword: Krebs ; Onkologie

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2015
• Creator: Haug, Stefan Peter Gustav
• Contributor: Zeiser, Robert

Further information

• DOI: 10.6094/UNIFR/10092
• URN: urn:nbn:de:bsz:25-freidok-100929
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:46 PM CET