Untersuchung des Einflusses von CA125 auf Chemoresistenz, Sphäroidbildung und Tumorstammzellmarkerexpression in Ovarialkarzinomzellen

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. Dabe...

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Bibliographic Details
Main Author: Kull, Eva
Contributors: Wagner, U. (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2017
Online Access:PDF Full Text
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Influence of CA125 on chemosensitivity, sphere formation and cancer stem cell markers in ovarian cancer cells Since the tumor associated antigen CA125 is commonly highly expressed in ovarian cancer cells, it is frequently used to monitor patients with ovarian cancer. To this day, the physiological role of this mucin is largely unknown. Therefore it is the aim of the present study to investigate the impact of CA125 gene silencing in ovarian cancer cells on its chemosensitivity, its ability to form spheres as well as on the expression of tumor stem cell markers. For this purpose, two subclones of the OAW42 cell line were used whose CA125 expression is significantly inhibited by means of stable transfection. In the present research study it was shown that adherent cells of the OAWH8+ cell line displayed a significantly higher carboplatin resistance, whereas paclitaxel resistance was unaffected by CA125 expression. In contrast, the OAWB8- cell line showed a divergent effect on carboplatin resistance. Here, CA125 gene silencing caused an increase of carboplatin sensitivity whereas it did not show any distinctive influence on paclitaxel. Furthermore the influence of CA125 gene silencing on the expression of cancer stem cell markers was investigated, but during the present studies no prove of any correlation could be found. Moreover CA125 expression increased the interaction between OAWB8- cells so that CA125+ cells showed an enhanced sphere formation compared to CA125- clones. With regard to the OAWB8- cell line, only the CA125- clone showed the ability to form spheres. In summary, for both cell lines it was observed that sphere forming cells showed an enhanced and significant resistance to carboplatin and paclitaxel compared to adherent cells. Especially in second line treatment of ovarian cancer chemoresistance is widespread. Moreover it seems that CA125 plays a central role in the survival of ovarian cancer cells. To establish new therapeutic approaches for curative therapy of ovarian cancer it should be further explored what mechanism and via which signaling pathways CA125 affects chemoresistance. Generally, extensive research on the physiological function of CA125 is necessary to develop new therapeutic options. In order to effectively identify tumor stem cells it furthermore remains to elicit ideal tumor stem cell markers. In the future, attention should particularly be focused on the question whether there is a change in CA125 expression in vivo and tumor stem cell properties in process of ovarian cancer. For this purpose, the withdrawal of sphere cells in ascites of ovarian cancer patients at initial diagnosis and in case of recidivation could be one methodic option.