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World J Stem Cells. Jul 26, 2021; 13(7): 861-876
Published online Jul 26, 2021. doi: 10.4252/wjsc.v13.i7.861
Reporter gene systems for the identification and characterization of cancer stem cells
Nohemí Salinas-Jazmín, Arely Rosas-Cruz, Marco Velasco-Velázquez
Nohemí Salinas-Jazmín, Arely Rosas-Cruz, Marco Velasco-Velázquez, Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
Author contributions: Salinas-Jazmín N, Rosas-Cruz A and Velasco-Velázquez M made substantial contributions to conception and design, compilation of published information, or interpretation of data; Salinas-Jazmín N, Rosas-Cruz A and Velasco-Velázquez M took part in drafting the article or revising it critically for important intellectual content; and gave final approval of the version to be published.
Supported by UNAM-PAPIIT, No. IN219719 and No. IA205421; CONACYT, No. A1-S-18285.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Marco Velasco-Velázquez, PhD, Professor, Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México, Av. Universidad 3000. Cd. Universitaria, Mexico City 04510, Mexico. marcovelasco@unam.mx
Received: March 8, 2021
Peer-review started: March 8, 2021
First decision: March 29, 2021
Revised: April 19, 2021
Accepted: July 5, 2021
Article in press: July 5, 2021
Published online: July 26, 2021
Processing time: 136 Days and 16.6 Hours
Abstract

Cancer stem cells (CSCs) are tumor cells that share functional characteristics with normal and embryonic stem cells. CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo- and radiotherapy, with important roles in tumor progression and the response to therapy. Thus, a current goal of cancer research is to eliminate CSCs, necessitating an adequate phenotypic and functional characterization of CSCs. Strategies have been developed to identify, enrich, and track CSCs, many of which distinguish CSCs by evaluating the expression of surface markers, the initiation of specific signaling pathways, and the activation of master transcription factors that control stemness in normal cells. We review and discuss the use of reporter gene systems for identifying CSCs. Reporters that are under the control of aldehyde dehydrogenase 1A1, CD133, Notch, Nanog homeobox, Sex-determining region Y-box 2, and POU class 5 homeobox can be used to identify CSCs in many tumor types, track cells in real time, and screen for drugs. Thus, reporter gene systems, in combination with in vitro and in vivo functional assays, can assess changes in the CSCs pool. We present relevant examples of these systems in the evaluation of experimental CSCs-targeting therapeutics, demonstrating their value in CSCs research.

Keywords: Cancer; Gene reporter systems; Cancer stem cells; Pluripotency transcription factors; Anticancer drugs; Preclinical analysis; Cancer stem cells marker

Core Tip: Controversial cancer stem cells (CSCs) research has caused confusion in this discipline. CSCs should be analyzed based on their function with regard to their ability to generate serially transplantable tumors. However, such evaluations are expensive and time-consuming and are fraught with ethical issues. Gene reporter assays can be used as a surrogate measure of the presence of CSCs in a sample. When combined with immunophenotyping and functional assays, reporter systems improve the quality of the evidence. However, there is no standard system; thus, the selection of an appropriate system must carefully consider its utility in previous works for the tumor type that is to be analyzed.