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Review
. 2016 Aug 26;8(8):260-7.
doi: 10.4252/wjsc.v8.i8.260.

Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

Minal Garg  1
Affiliations
Review

Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

Minal Garg. World J Stem Cells. .

Abstract

Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells.

Keywords: Cancer stem cells; Clinical management; Cytotoxic effects; Epithelial plasticity; Therapeutic resistance; Urothelial carcinoma; Urothelial stem cells.

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Figures

Figure 1
Figure 1
Staging, grading and prognosis of urothelial carcinoma of the bladder.
Figure 2
Figure 2
Multimodality approaches for urothelial carcinoma of the bladder. NMIBC: Non-muscle invasive bladder cancer; MIBC: Muscle invasive bladder cancer.
Figure 3
Figure 3
Cellular differentiation and mutational transformation of urothelial stem cells and dual pathways of carcinogenesis. A: Cellular differentiation of UroSCs (exist in the form of clonal patches in basal layer) gives rise to basal cells which further differentiate to intermediate cells and then into single layer of umbrella cells; B: Mutational insults including epithelial plasticity result in malignant transformation of UroSCs into self-renewing UroCSCs which undergo aberrant activation and differentiation to form papillary non muscle invasive and muscle invasive bladder cancer; C: In vivo xenotransplantation of a small number of UroCSCs that have the potential for the regrowth of heterogeneous tumor cells. UroCSCs: Urothelial cancer stem cells; NMIBC: Non-muscle invasive bladder cancer; MIBC: Muscle invasive bladder cancer.
Figure 4
Figure 4
Epithelial mesenchymal transition and mesenchymal epithelial transition in urothelial carcinoma. EMT/epithelial plasticity allows invasive bladder cancer cells to become motile, invade the surrounding tissues and intravasate. Through bloodstream, primary tumor cells move to distant sites, extravasate, colonize the target organs and establish the metastasis. MET induces regrowth and re-establishment of cancer cells with epithelial phenotype at secondary/metastatic sites. EMT: Epithelial mesenchymal transition; MET: Mesenchymal epithelial transition.
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References

    1. Van Batavia J, Yamany T, Molotkov A, Dan H, Mansukhani M, Batourina E, Schneider K, Oyon D, Dunlop M, Wu XR, et al. Bladder cancers arise from distinct urothelial sub-populations. Nat Cell Biol. 2014;16:982–991, 1-5. - PubMed
    1. Amin MB. Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications. Mod Pathol. 2009;22 Suppl 2:S96–S118. - PubMed
    1. Shuto M, Warigaya K, Watanabe H, Shimizu M, Fukuda T, Murata S. Correlation analysis of nuclear morphology, cytokeratin and Ki-67 expression of urothelial carcinoma cells. Pathol Int. 2013;63:311–317. - PubMed
    1. Dancik GM, Owens CR, Iczkowski KA, Theodorescu D. A cell of origin gene signature indicates human bladder cancer has distinct cellular progenitors. Stem Cells. 2014;32:974–982. - PMC - PubMed
    1. Moad M, Pal D, Hepburn AC, Williamson SC, Wilson L, Lako M, Armstrong L, Hayward SW, Franco OE, Cates JM, et al. A novel model of urinary tract differentiation, tissue regeneration, and disease: reprogramming human prostate and bladder cells into induced pluripotent stem cells. Eur Urol. 2013;64:753–761. - PMC - PubMed

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