Interferon-gamma inhibits aldehyde dehydrogenase^(bright)cancer stem cells in the 4T1 mouse model of breast cancer  

作　　者：Xiufen Zhuang Guilan Shi Xiao Hu Huiru Wang Wen Sun Yanhong Wu 

机构地区：[1]Department of Oncology,Affiliated Hospital of Jiangsu University,Zhenjiang,Jiangsu 212000,China [2]Department of Immunology,Zibo Vocational Institute Health School,Zibo,Shandong 255000,China [3]Department of Medical Engineering,Morsani College of Medicine,Tampa,FL 33612,USA [4]Department of Oncology,Suqian First Hospital,Suqian,Jiangsu 223800,China [5]Department of Blood Transfusion,The First Affiliated Hospital of USTC,Hefei,Anhui 230001,China [6]Department of Medical Microbiology and Immunology,School of Basic Medical Sciences,Wannan Medical College,Wuhu,Anhui 241002,China.

出　　处：《Chinese Medical Journal》2022年第2期194-204,共11页中华医学杂志（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.81402442 and No.81903637);the Fundamental Research Funds for the Central Universities(WK9110000027).

摘　　要：Background:Despite improvements in disease diagnosis,treatment,and prognosis,breast cancer is still a leading cause of cancer death for women.Compelling evidence suggests that targeting cancer stem cells(CSCs)have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy.In the present study,we aimed to study the effects of T cells and a critical anti-tumor cytokine,interferon-gamma(IFN-γ),on breast cancer stem cells.Methods:BALB/c mice and BALB/c nude mice were subcutaneously injected with 4T1 tumor cells.Tumor growth and pulmonary metastasis were assessed.ALDEFLOUR™assays were performed to identify aldehyde dehydrogenase^(bright)(ALDH^(br))tumor cells.ALDH^(br)cells as well as T cells from tumor-bearing BALB/c mice were analyzed using flow cytometry.The effects of CD8^(+)T cells on ALDH^(br)tumor cells were assessed in vitro and in vivo.The expression profiles of ALDH^(br)and ALDH^(dim)4T1 tumor cells were determined.The levels of plasma IFN-γwere measured by enzyme-linked immunosorbent assay,and their associations with the percentages of ALDH^(br)tumor cells were evaluated.The effects of IFN-γon ALDH expression and the malignancy of 4T1 tumor cells were analyzed in vitro.Results:There were fewer metastatic nodules in tumor-bearing BALB/c mice than those in tumor-bearing BALB/c nude mice(25.40 vs.54.67,P<0.050).CD8^(+)T cells decreased the percentages of ALDH^(br)4T1 tumor cells in vitro(control vs.effector to target ratio of 1:1,10.15%vs.5.76%,P<0.050)and in vivo(control vs.CD8^(+)T cell depletion,10.15%vs.21.75%,P<0.001).The functions of upregulated genes in ALDH^(br)4T1 tumor cells were enriched in the pathway of response to IFN-γ.The levels of plasma IFN-γdecreased gradually in tumor-bearing BALB/c mice,while the percentages of ALDH^(br)tumor cells in primary tumors increased.IFN-γat a concentration of 26.68 ng/mL decreased the percentages of ALDH^(br)4T1 tumor cells(22.88%vs.9.88%,P<0.050)and the protein levels of aldehyde dehydrogenase 1 family member A1 in 4T1 tumor

关 键 词：Cancer stem cells Aldehyde dehydrogenase INTERFERON-GAMMA CD8+T cells 

分 类 号：R737.9[医药卫生—肿瘤]