Publikationsserver der Universitätsbibliothek Marburg
Titel:Untersuchung des Einflusses von CA125 auf Chemoresistenz, Sphäroidbildung und Tumorstammzellmarkerexpression in Ovarialkarzinomzellen
Autor:Kull, Eva
Weitere Beteiligte: Wagner, U. (Prof. Dr.)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0295
DOI: https://doi.org/10.17192/z2017.0295
URN: urn:nbn:de:hebis:04-z2017-02957
DDC: Medizin
Titel (trans.):Influence of CA125 on chemosensitivity, sphere formation and cancer stem cell markers in ovarian cancer cells
Publikationsdatum:2017-05-03
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
Sphäroide, CD117, CD133, CD24, CD22, ALDH, Ovarialkarzinom, Ovarian Cancer, Tumostammzellmarker, CA125, MUC16, Chemoresistenz

Zusammenfassung:
Einfluss von CA125 auf Chemoresistenz, Sphäroidbildung und Tumorstammzellmarkerexpression in Ovarialkarzinomzellen Das tumorassoziierte Antigen CA125 wird häufig zur Verlaufskontrolle von Patientinnen mit Ovarialkarzinom angewendet, da es in Ovarialkarzinomzellen zumeist überexprimiert wird. Dabei ist die physiologische Funktion des Muzins bis heute weitgehend unbekannt. Ziel dieser Arbeit ist es daher, zu untersuchen, welchen Einfluss der Knockdown von CA125 in Ovarialkarzinomzellen auf die Chemosensibilität der Zellen, die Fähigkeit zu Sphäroidbildung sowie auf die Expression von Tumorstammzellmarkern besitzt. Zu diesem Zweck wurden zwei Subklone der Zelllinie OAW42 verwendet, deren CA125-Expression mittels stabiler Transfektion signifikant gehemmt wird. In dieser Arbeit konnte gezeigt werden, dass die adhärenten Zellen der Zelllinie OAWH8+ durch den CA125 Knockdown eine signifikant höhere Carboplatinresistenz besitzen, wohingegen die Paclitaxelresistenz durch die CA125 Expression unbeeinflusst bleibt. In der Zelllinie OAWB8- hingegen bewirkte der CA125 Knockdown einen gegenteiligen Effekt bezüglich der Carboplatinresistenz, so dass der CA125 Knockdown hier zu einer Erhöhung der Carboplatinsensibilität führte. Gegenüber Paclitaxel hatte CA125 wiederum keinen markanten Einfluss. Weiterhin wurde der Einfluss des CA125 Knockdowns auf die Expression von Tumorstammzellmarkern untersucht, wobei sich bei den Versuchen dieser Arbeit kein Zusammenhang nachweisen lässt. Zudem verstärkte die CA125 Expression die homotypische Interaktion der OAWB8- Zellen, sodass CA125+ Zellen eine stärkere Sphäroidbildung zeigten als die CA125- Knockdownklone. Für die Zelllinie OAWB8- zeigte hingegen nur der CA125- OAWB8- Knockdownklon die Fähigkeit zur Sphäroidbildung. Zusammenfassend konnte für beide Zelllinien beobachtet werden, dass die Zellen in Sphäroidkultur eine deutlichere Resistenz gegenüber Carboplatin und Paclitaxel aufwiesen, als die adhärenten Kontrollzellen. Besonders in der Sekundärtherapie des Ovarialkarzinoms sind Chemoresistenzen weit verbreitet. Dabei scheint CA125 eine zentrale Rolle für das Überleben von Ovarialkarzinomzellen einzunehmen. Mit welchem Mechanismus und über welche Signalmoleküle CA125 die Chemoresistenz beeinflusst, sollte daher weiter erforscht werden, um langfristig einen neuen Therapieansatz für eine kurative Therapie des Ovarialkarzinoms zu etablieren. Generell bedarf es zur Entwicklung weiterer Therapieoptionen einer umfangreichen Erforschung der physiologischen Funktion von CA125. Des Weiteren bleibt die Detektion optimaler Tumorstammzellmarker für Ovarialkarzinomzellen zu eruieren, um Tumorstammzellen effektiv identifizieren zu können. Dabei sollte in Zukunft insbesondere der Frage nachgegangen werden, ob sich im Verlauf einer Ovarialkarzinomerkrankung auch in vivo eine Veränderung der CA125 Expression sowie der Tumorstammzellanteile beobachten lässt. Hierfür würde sich besonders die Entnahme von Sphäroidzellen im Aszites von Ovarialkarzinompatientinnen nach Erstdiagnose sowie gegebenenfalls bei Auftreten eines Rezidivs eignen.

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