Opinion Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2021; 13(2): 92-108
Published online Feb 15, 2021. doi: 10.4251/wjgo.v13.i2.92
Could gastrointestinal tumor-initiating cells originate from cell-cell fusion in vivo?
Yang Zhou, Jun-Ting Cheng, Zi-Xian Feng, Ying-Ying Wang, Ying Zhang, Wen-Qi Cai, Zi-Wen Han, Xian-Wang Wang, Ying Xiang, Hui-Yu Yang, Bing-Rong Liu, Xiao-Chun Peng, Shu-Zhong Cui, Hong-Wu Xin
Yang Zhou, Jun-Ting Cheng, Ying-Ying Wang, Ying Zhang, Wen-Qi Cai, Zi-Wen Han, Xian-Wang Wang, Ying Xiang, Xiao-Chun Peng, Hong-Wu Xin, Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, Hubei Province, China
Yang Zhou, Jun-Ting Cheng, Ying-Ying Wang, Ying Zhang, Wen-Qi Cai, Zi-Wen Han, Xian-Wang Wang, Ying Xiang, Hong-Wu Xin, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, Hubei Province, China
Zi-Xian Feng, Department of Oncology and Haematology, Lianjiang People's Hospital, Guangzhou 524400, Guangdong Province, China
Hui-Yu Yang, Bing-Rong Liu, Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
Xiao-Chun Peng, Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, Hubei Province, China
Shu-Zhong Cui, State Key Laboratory of Respiratory Disease, Affiliated Cancer Hospital Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong Province, China
Author contributions: Zhou Y, Cheng JT, and Feng ZX contributed equally to the manuscript; Zhou Y, Peng XC, Cui SZ, and Xin HW conducted the research design; Zhou Y conducted the literature retrieval; Zhang Y participated in manuscript drafting; Peng XC, Cui SZ, and Xin HW conducted the final review of the manuscript; all the authors were involved in the revision and editing of the manuscript.
Supported by National Natural Science Foundation of China, No. 81872412, No. 81602303, and No. 31700736; Hubei Province Natural Science Foundation of China, No. 2016CFB180 and No. 2017CFB786; Health and Family Planning Commission of Hubei Province, No. WJ2016Y07 and No. WJ2016Y10; Hubei Province Scientific and Technological Research Project, No. Q20171306; Jingzhou Science and Technology Development Planning Project, No. JZKJ15063; Guangzhou Key Medical Discipline Construction Project (CSZ), National Innovation and Entrepreneurship Training Program for College Students, No. 202010489017.
Conflict-of-interest statement: All the authors have no conflicts of interest to declare.
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: Hong-Wu Xin, PhD, MD, Doctor, Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, No. 1 Nanhuan Road, Jingzhou 434023, Hubei Province, China. hongwu_xin@126.com
Received: October 30, 2020
Peer-review started: October 30, 2020
First decision: December 12, 2020
Revised: December 25, 2020
Accepted: January 28, 2021
Article in press: January 28, 2021
Published online: February 15, 2021
Processing time: 93 Days and 23.4 Hours
Abstract

Tumor-initiating cells (TICs) or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation, progression, metastasis, and drug resistance. It is hypothesized that gastrointestinal TICs (giTICs) might originate from cell-cell fusion. Here, we systemically evaluate the evidence that supports or opposes the hypothesis of giTIC generation from cell-cell fusion both in vitro and in vivo. We review giTICs that are capable of initiating tumors in vivo with 5000 or fewer in vivo fused cells. Under this restriction, there is currently little evidence demonstrating that giTICs originate from cell-cell fusion in vivo. However, there are many reports showing that tumor generation in vitro occurs with more than 5000 fused cells. In addition, the mechanisms of giTIC generation via cell-cell fusion are poorly understood, and thus, we propose its potential mechanisms of action. We suggest that future research should focus on giTIC origination from cell-cell fusion in vivo, isolation or enrichment of giTICs that have tumor-initiating capabilities with 5000 or less in vivo fused cells, and further clarification of the underlying mechanisms. Our review of the current advances in our understanding of giTIC origination from cell-cell fusion may have significant implications for the understanding of carcinogenesis and future cancer therapeutic strategies targeting giTICs.

Keywords: Gastrointestinal tumor-initiating cell; Stem cell; Bone marrow-derived cells; In vivo; Cell-cell fusion; In vitro

Core Tip: Currently, there are many controversial hypotheses concerning the generation of gastrointestinal tumor-initiating cells (giTICs). Here, we mainly review the current advances in the understanding of giTIC origination from the cell-cell fusion of cancer cells and bone marrow-derived cells.