机构：[1]Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China[2]Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, China[3]College of Forensic Medicine, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Medical University, Shijiazhuang, China[4]Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China河北医科大学第四医院胸五科临床科室
Cancer stem cells (CSCs) give rise to a diverse variety of differentiated cells, which comprise the bulk of the tumor microenvironment (TME). However, the exact multi-directional differentiation potential of CSCs has not been fully clarified. This study was designed to explore whether CSCs differentiate into cellular components of the TME to promote the growth of lung carcinoma.
The present of CD133+, CD2+, and CD133+CD2+ cells in both clinical lung adenocarcinoma tissue and non-small cell lung carcinoma (NSCLC) cell lines were monitored using polymerase chain reaction (PCR) Array, flow cytometry (FCM), quantitative real-time PCR (qRT-PCR) and immunohistofluorescence (IF). Stem-like properties of CD133+ cells and CD2+ cells were detected by sphere formation assay, IF, and western blot. Colony formation and xenograft tumors experiments were performed to assess the malignant behaviors of CD2+ cells. The differentiation of CD133+ cells to CD2+ Th17-like cells was observed by FCM. The interleukin (IL)-2/phosphorylated signal transducer and activator of transcription protein 5 (pSTAT5)/retinoic acid receptor-related orphan receptor gamma t (RORγt) signaling pathway was evaluated by western blot and FCM.
We found that CD133+ cells within both clinical lung adenocarcinoma tissue and NSCLC cell lines included a subset of CD2-expressing cells, which were correlated with the grade of malignancy (r=0.7835, P<0.01) and exhibited stem-like properties. Then, we determined the tumorigenic effects of CD2 on the growth of transplanted Lewis lung carcinoma cells (LLC1) in C57/BL6 mice. The results indicated that CD2+ cells were effective in promoting tumor growth in vivo (P<0.01). Furthermore, we obtained direct evidence of an ability of CD133+ cells to transform to T-helper 17-like cells via an intermediate CD133+CD2+ progenitor cell that is able to secrete IL-17A and IL-23. Furthermore, we found that IL-2 can inhibit the production of T-helper 17-like cells (P<0.001) by modulating the activation of STAT5 signaling pathways to downregulate the expression of RORγt (P<0.001).
Our data demonstrates that Th17-like cells generated from CSCs support cancer progression. These findings enrich the definition of multidirectional differentiation potential of CSCs and improve the understanding of the role of CSCs in cancer progression, which aids the improvement and creation of therapies.
2021 Annals of Translational Medicine. All rights reserved.
基金：
Colleges and Universities in Hebei Province Scientific Research Project High Level Talents Fund [GCC2014004]; CAMS Innovation Fund for Medical Sciences [2019-12M-5055]; Natural Science Foundation of Hebei ProvinceNatural Science Foundation of Hebei Province [H2020206579]; Key Research and Development Program of Hebei Province [20327125D]
第一作者机构：[1]Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China[2]Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, China
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China[2]Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, China[3]College of Forensic Medicine, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Medical University, Shijiazhuang, China[*1]Institute of basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, China.
推荐引用方式(GB/T 7714)：
Jia Miaomiao,Jia Xianxian,Zhang Dong,et al.CD2+ T-helper 17-like cells differentiated from a CD133+ subpopulation of non-small cell lung carcinoma cells promote the growth of lung carcinoma.[J].ANNALS OF TRANSLATIONAL MEDICINE.2021,9(8):doi:10.21037/atm-21-980.
APA：
Jia Miaomiao,Jia Xianxian,Zhang Dong,Liu Wenxuan,Yi Shanyong...&Zhang Jun.(2021).CD2+ T-helper 17-like cells differentiated from a CD133+ subpopulation of non-small cell lung carcinoma cells promote the growth of lung carcinoma..ANNALS OF TRANSLATIONAL MEDICINE,9,(8)
MLA：
Jia Miaomiao,et al."CD2+ T-helper 17-like cells differentiated from a CD133+ subpopulation of non-small cell lung carcinoma cells promote the growth of lung carcinoma.".ANNALS OF TRANSLATIONAL MEDICINE 9..8(2021)
