Am J Stem Cell 2013;2(1):52-61

Review Article
Cancer stem cells and tumor transdifferentiation: implications for novel therapeutic
strategies

Mohammed Talha Shekhani, Ashika-Sita Jayanthy, Nityanand Maddodi, Vijayasaradhi Setaluri

University of Wisconsin School of Medicine & Public Health, Department of Dermatology, Madison, Wisconsin 53706, USA

Received December 24, 2012; Accepted February 15, 2013; Epub March 8, 2013; Published March 18, 2013

Abstract: Highly malignant tumors mostly consist of rapidly proliferating cells. However, tumors also contain a few cells in a quiescent
state that can be characterized as slow-cycling, expressing markers of stem cells and possessing the ability to initiate new tumors.
These quiescent cells, now generally termed ‘cancer stem cells’ (CSC) (or ‘cancer initiating cells’), are capable of regenerating the entire
tumor—as it occurs in metastatic spread. This process of tumor initiation by stem-like cells presumably involves differentiation of
quiescent CSC into rapidly proliferating tumor cells. An important implication of the presence of slow cycling, quiescent stem-like cells in
the tumor and their ability to initiate tumors is that they contribute to the resistance to treatments by conventional chemo- and radiotherapy
directed toward killing rapidly dividing cells. However, similar to normal stem cells, the CSC could also potentially transdifferentiate into
cell lineages other than the original lineage from which the tumor arose. Therefore, transdifferentiation of CSC offers a possible
therapeutic strategy which has not yet been fully exploited. In this article, we provide a comprehensive review of the concepts in tumor cell
transdifferentiation and discuss the mechanisms of transdifferentiation with emphasis on their relevance to potential novel treatment
strategies. (AJSC1212003).

Keywords: Cancer stem cells, transdifferentiation, CSC-targeted therapy, tumor Initiating cell, EMT

Address correspondence to: Dr. Vijayasaradhi Setaluri, University of Wisconsin School of Medicine & Public Health, Department of
Dermatology, Madison, Wisconsin 53706, USA. E-mail: vsetaluri@dermatology.wisc.edu
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