title: IFN-γ selectively exerts pro-apoptotic effects on tumor-initiating label-retaining colon cancer cells.
abstract: Label-retaining cancer cells (LRCCs) represent a novel population of stem-like cancer cells exhibiting slow cycling, chemoresistance and tumor-initiating capacities; however, their properties remain unclear, and approaches to eradicate LRCCs remain elusive. Here, we report that colon cancer cells with high fluorescent intensity, referred to as LRCCs, have the greatest cancer stem cell (CSC)-like capacities and that they preferentially express CSC markers and stemness-related genes. Moreover, we found that Lgr5, which has been reported to be a marker of rapid cycling CSCs, is almost negatively expressed in LRCCs but that its expression is gradually increased in the differentiation process of LRCCs. Interestingly, we found that LRCCs are especially sensitive to the pro-apoptotic effect of IFN-γ treatment both in vitro and in vivo because LRCCs possess higher IFN-γR levels compared with non-LRCCs, which results in the upregulation of the apoptosis pathway after IFN-γ treatment. Furthermore, we found that IFN-γ shows synergistic effects with the conventional anticancer drug Oxaliplatin to eliminate both LRCCs and non-LRCCs. In conclusion, this is the first study to suggest that LRCCs, as a distinct tumor-initiating population, can be selectively eradicated by IFN-γ, which may provide a novel therapeutic strategy for colon cancer treatment.
authors: Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors: Chao
authors: C
authors: Ni
authors: Ping
authors: P
authors: Wu
authors: Xiaotao
authors: X
authors: Zhu
authors: Jun
authors: J
authors: Ye
authors: Zhigang
authors: Z
authors: Zhang
authors: Zhigang
authors: Z
authors: Chen
authors: Ting
authors: T
authors: Zhang
authors: Tao
authors: T
authors: Zhang
authors: Ke
authors: K
authors: Wang
authors: Dang
authors: D
authors: Wu
authors: Fuming
authors: F
authors: Qiu
authors: Jian
authors: J
authors: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002469:Cell Separation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology
chemical_list: C116884:LGR5 protein, human; D009944:Organoplatinum Compounds; D043562:Receptors, G-Protein-Coupled; D000077150:Oxaliplatin; D007371:Interferon-gamma