Ovarian Cancer Stem Cell Heterogeneity
Ovarian carcinoma features pronounced clinical, histopathological, and molecular heterogeneity. There is good reason to believe that parts of this heterogeneity can be explained by differences in the respective cell of origin, with a self-renewing fallopi
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Ovarian Cancer Stem Cell Heterogeneity Jiri Hatina, Maximilian Boesch, Sieghart Sopper, Michaela Kripnerova, Dominik Wolf, Daniel Reimer, Christian Marth, and Alain G. Zeimet
Abstract Ovarian carcinoma features pronounced clinical, histopathological, and molecular heterogeneity. There is good reason to believe that parts of this heterogeneity can be explained by differences in the respective cell of origin, with a self- renewing fallopian tube secretory cell being likely responsible for initiation of an overwhelming majority of high-grade serous ovarian carcinomas (i.e., type II tumors according to the recent dualistic classification), whereas there are several mutually non-exclusive possibilities for the initiation of type I tumors, including ovarian surface epithelium stem cells, endometrial cells, or even cells of extra-Müllerian origin. Interestingly, both fallopian tube self-renewing secretory cells and ovarian surface epithelium stem cells seem to be characterized by an overlapping array of stemness signaling pathways, especially Wnt/β-catenin. Apart from this variability in the respective cell of origin, the particular clinical behavior of ovarian carcinoma strongly suggests an underlying stem cell component with a crucial impact. This becomes especially evident in high-grade serous ovarian carcinomas treated with
Jiri Hatina and Maximilian Boesch contributed equally to this work. J. Hatina · M. Kripnerova Faculty of Medicine in Pilsen, Institute of Biology, Charles University, Pilsen, Czech Republic e-mail: [email protected] M. Boesch Lungenzentrum, Kantonsspital St. Gallen, St. Gallen, Switzerland S. Sopper Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria Tyrolean Cancer Research Institute, Innsbruck, Austria D. Wolf Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria D. Reimer · C. Marth · A. G. Zeimet (*) Department of Gynecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria e-mail: [email protected] © Springer Nature Switzerland AG 2019 A. Birbrair (ed.), Stem Cells Heterogeneity in Cancer, Advances in Experimental Medicine and Biology 1139, https://doi.org/10.1007/978-3-030-14366-4_12
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classical chemotherapy, which entails a gradual evolution of c hemoresistant disease without any apparent selection of clones carrying obvious chemoresistance- associated mutations. Several cell surface markers (e.g., CD24, CD44, CD117, CD133, and ROR1) as well as functional approaches (ALDEFLUOR™ and side population assays) have been used to identify and characterize putative ovarian carcinoma stem cells. We have recently shown that side population cells exhibit marked heterogeneity on their own, which can hamper their straightforward therapeutic targeting. An alternative strategy for stemness-depleting interventions is to target the stem cell niche, i.e., the specific microanatomical structure that secures stem cell maintenance and survival through provision of a set of stem cell-promoting and differentia
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