Urothelial Cancer Stem Cell Heterogeneity
Urothelial carcinoma is a tumor type featuring pronounced intertumoral heterogeneity and a high mutational and epigenetic load. The two major histopathological urothelial carcinoma types – the non-muscle-invasive and muscle-invasive urothelial carcinoma –
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Urothelial Cancer Stem Cell Heterogeneity Michaela Kripnerova, Hamendra Singh Parmar, Martin Pesta, Michaela Kohoutova, Jitka Kuncova, Karel Drbal, Marie Rajtmajerova, and Jiri Hatina
Abstract Urothelial carcinoma is a tumor type featuring pronounced intertumoral heterogeneity and a high mutational and epigenetic load. The two major histopathological urothelial carcinoma types – the non-muscle-invasive and muscle-invasive urothelial carcinoma – markedly differ in terms of their respective typical mutational profiles and also by their probable cells of origin, that is, a urothelial basal cell for muscle-invasive carcinomas and a urothelial intermediate cell for at least a large part of non-muscle-invasive carcinomas. Both non-muscle-invasive and muscle- invasive urothelial carcinomas can be further classified into discrete intrinsic subtypes based on their typical transcriptomic profiles. Urothelial carcinogenesis shows a number of parallels to a urothelial regenerative response. Both of these processes seem to be dominated by specific stem cell populations. In the last years, the nature and location of urothelial stem cell(s) have been subject to many controversies, which now seem to be settled down, favoring the existence of a largely single urothelial stem cell type located among basal cells. Basal cell markers have also been amply used to identify urothelial carcinoma stem cells, especially in muscle-invasive disease, but they proved useful even in some non-muscle-invasive tumors. Analyses on molecular nature of urothelial carcinoma stem cells performed till now point to their great heterogeneity, both during the tumor development and upon intertumoral
M. Kripnerova · M. Pesta · J. Hatina (*) Charles University, Faculty of Medicine in Pilsen, Institute of Biology, Pilsen, Czech Republic e-mail: [email protected] H. S. Parmar Charles University, Faculty of Medicine in Pilsen, Institute of Biology, Plzen, Czech Republic School of Biotechnology, Devi Ahilya University, Indore, MP, India M. Kohoutova · J. Kuncova Charles University, Faculty of Medicine in Pilsen, Institute of Physiology, Plzen, Czech Republic K. Drbal · M. Rajtmajerova Charles University, Faculty of Science, Department of Cell Biology, Prague, Czech Republic © 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_8
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comparison, sexual dimorphism providing a special example of the latter. Moreover, urothelial cancer stem cells are endowed with intrinsic plasticity, whereby they can modulate their stemness in relation to other tumor-related traits, especially motility and invasiveness. Such transitional modulations suggest underlying epigenetic mechanisms and, even within this context, inter- and intratumoral heterogeneity becomes apparent. Multiple molecular aspects of urothelial cancer stem cell biology markedly influence therapeutic response, implying their knowledge as a prer
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