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Ovarian Cancer Stem Cell Heterogeneity

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Stem Cells Heterogeneity in Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1139))

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 classical chemotherapy, which entails a gradual evolution of chemoresistant 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 differentiation-antagonizing factors. Besides identifying direct or indirect therapeutic targets, profiling of side population cells and other ovarian carcinoma stem cell subpopulations can reveal relevant prognostic markers, as exemplified by our recent discovery of the Vav3.1 transcript variant, which filters out a fraction of prognostically unfavorable ovarian carcinoma cases.

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Acknowledgements

This work was supported by the Austrian Research Promotion Agency (FFG) under Grant 858057 (HD FACS) and COMET Center Oncotyrol and by the Charles University in Prague Specific Student Research Project Nr. 260393/2017.

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Author notes

  1. Jiri Hatina and Maximilian Boesch contributed equally to this work.

Authors and Affiliations

  1. Faculty of Medicine in Pilsen, Institute of Biology, Charles University, Pilsen, Czech Republic

    Jiri Hatina & Michaela Kripnerova

  2. Lungenzentrum, Kantonsspital St. Gallen, St. Gallen, Switzerland

    Maximilian Boesch

  3. Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria

    Sieghart Sopper & Dominik Wolf

  4. Tyrolean Cancer Research Institute, Innsbruck, Austria

    Sieghart Sopper

  5. Department of Gynecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria

    Daniel Reimer, Christian Marth & Alain G. Zeimet

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  1. Jiri Hatina
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  2. Maximilian Boesch
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  3. Sieghart Sopper
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  4. Michaela Kripnerova
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  5. Dominik Wolf
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  6. Daniel Reimer
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  7. Christian Marth
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  8. Alain G. Zeimet
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Corresponding author

Correspondence to Alain G. Zeimet .

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Editors and Affiliations

  1. Department of Pathology, Federal University of Minas Gerais, Department of Radiology, Columbia University Medical Center, New York, NY, USA, Belo Horizonte, MG, Brazil

    Alexander Birbrair

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Hatina, J. et al. (2019). Ovarian Cancer Stem Cell Heterogeneity. In: Birbrair, A. (eds) Stem Cells Heterogeneity in Cancer. Advances in Experimental Medicine and Biology, vol 1139. Springer, Cham. https://doi.org/10.1007/978-3-030-14366-4_12

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