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World J Stem Cells. Aug 26, 2016; 8(8): 260-267
Published online Aug 26, 2016. doi: 10.4252/wjsc.v8.i8.260
Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges
Minal Garg
Minal Garg, Department of Biochemistry, University of Lucknow, Lucknow 226007, India
Author contributions: Garg M solely contributed to this paper.
Supported by Department of Science and Technology, Govt. of India, No. SR/H0/HS/0113-2010.
Conflict-of-interest statement: The author declares no potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Minal Garg, Msc, PhD, Assistant Professor, Department of Biochemistry, University of Lucknow, University Road, Lucknow 226007, India. minal14@yahoo.com
Telephone: +91-9335-820857
Received: March 20, 2016
Peer-review started: March 22, 2016
First decision: April 20, 2016
Revised: April 25, 2016
Accepted: June 27, 2016
Article in press: June 29, 2016
Published online: August 26, 2016
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

Core tip: A subset of bladder cancer cells, known as urothelial cancer stem cells, have abilities to self-renew, generate tumor heterogeneity via differentiation, and are actually responsible for tumor relapse and metastasis formation. Delineating the mechanistic complexity between epithelial plasticity and cancer stemness in malignant transformation of urothelial carcinoma provides the basis for designing rational therapies. Differentiation and elimination therapies targeting the potential biomarkers could prove to be clinically beneficial by suppressing the cancer stemness and inhibiting epithelial-to-mesenchymal transition phenotype and would provide novel opportunities for targeted therapeutic approaches in the clinical management of patients.