摘要
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.
基金
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。
