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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2015; 7(1): 27-36
Published online Jan 26, 2015. doi: 10.4252/wjsc.v7.i1.27
Cancer stem cell plasticity and tumor hierarchy
Marina Carla Cabrera, Robert E Hollingsworth, Elaine M Hurt
Marina Carla Cabrera, Robert E Hollingsworth, Elaine M Hurt, MedImmune, LLC, Department of Oncology Research, Gaithersburg, MD 20878, United States
Author contributions: All authors contributed to writing and review of the manuscript.
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: Elaine M Hurt, PhD, MedImmune, LLC, Department of Oncology Research, 1 MedImmune Way, Gaithersburg, MD 20878, United States. hurte@medimmune.com
Telephone: +1-301-3985688 Fax: +1-301-3987735
Received: August 1, 2014
Peer-review started: August 2, 2014
First decision: August 28, 2014
Revised: September 23, 2014
Accepted: October 23, 2014
Article in press: December 16, 2014
Published online: January 26, 2015
Processing time: 166 Days and 9.6 Hours
Abstract

The origins of the complex process of intratumoral heterogeneity have been highly debated and different cellular mechanisms have been hypothesized to account for the diversity within a tumor. The clonal evolution and cancer stem cell (CSC) models have been proposed as drivers of this heterogeneity. However, the concept of cancer stem cell plasticity and bidirectional conversion between stem and non-stem cells has added additional complexity to these highly studied paradigms and may help explain the tumor heterogeneity observed in solid tumors. The process of cancer stem cell plasticity in which cancer cells harbor the dynamic ability of shifting from a non-CSC state to a CSC state and vice versa may be modulated by specific microenvironmental signals and cellular interactions arising in the tumor niche. In addition to promoting CSC plasticity, these interactions may contribute to the cellular transformation of tumor cells and affect response to chemotherapeutic and radiation treatments by providing CSCs protection from these agents. Herein, we review the literature in support of this dynamic CSC state, discuss the effectors of plasticity, and examine their role in the development and treatment of cancer.

Keywords: Cancer stem cells; Stem cell; Plasticity; Tumor hierarchy; Microenvironment; Immune-mediated therapies; Epithelial-to-mesenchymal transition

Core tip: The origins of the complex process of intratumoral heterogeneity have been highly debated and different cellular mechanisms have been hypothesized to account for the diversity within a tumor. The clonal evolution and cancer stem cell (CSC) models have been proposed as drivers of this heterogeneity. However, the concept of cancer stem cell plasticity and bidirectional conversion between stem and non-stem cells has added additional complexity to these highly studied paradigms and may help explain the tumor heterogeneity observed in solid tumors. Herein, we review the literature in support of this dynamic CSC state, discuss the effectors of plasticity, and examine their role in the development and treatment of cancer.