Research advances in the mechanisms of tumor stem cells on the radiotherapy effects of NSCLC

doi:10.3877/cma.j.issn.2095-1221.2020.03.007

Abstract

Abstract:

Cancer stem cell (CSC) is a kind of cell subpopulation with the tumor initiation potential, self-renewal and unlimited proliferation. It is closely related to local recurrence and distant metastasis of tumors as well as the root cause of resistance to radiotherapy. Non-small-cell lung cancer is a malignant tumor with high incidence and mortality rate. It has been confirmed that CSC subsets with stem cell characteristics in non-small-cell lung cancer. At present, CSCs of non-small-cell lung cancer are mainly obtained by isolating a series of cells with immunophenotypes such as CD133. CSC mediates the radiotherapy resistance of non-small-cell lung cancer through mechanisms such as DNA damage, cell autophagy, and hypoxic tumor microenvironment. In this review, the biological characteristics, immunophenotypic expression and the molecular mechanism of radiotherapy resistance of CSC in non-small-cell lung cancer were reviewed in order to provide relevant evidence for the improvement of radiotherapy efficacy in non-small -cell lung cancer.

Key words: Cancer stem cells, Non-small-cell lung cancer, Radiotherapy

Huanyu He, Xiao Jiang, Kunming Zhang, Yukun Yang, Mao Wang, Yi Li. Research advances in the mechanisms of tumor stem cells on the radiotherapy effects of NSCLC[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2020, 10(03): 177-181.

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References 62

1	郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1):19-28.
2	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016[J]. CA Cancer J lin, 2016, 66(1):7-30.
3	Ettinger DS, Wood D, Akerley W, et al. NCCN guidelines insights: non-small cell lung cancer, version 4.2016[J]. J Natl Compr Canc Netw, 2016, 14(3):255-264.
4	Dreyer J, Bremer M, Henkenberens C. Comorbidity indexing for prediction of the clinical outcome after stereotactic body radiation therapy in non-small cell lung cancer[J]. Radiat Oncol, 2018, 13(1):1-8.
5	Brooks ED, Verma V, Senan S, et al. Salvage Therapy for Locoregional Recurrence After Stereotactic Ablative Radiotherapy for Early-Stage NSCLC[J]. J Thorac Oncol, 2020, 15(2):176-189.
6	Moharil RB, Dive A, Khandekar S, et al. Cancer stem cells: An insight[J]. J Oral Maxillofac Pathol, 2017, 21(3):463-469.
7	Rabata A, Hampl A, Koledova Z. Lungosphere assay: 3D culture of lung epithelial stem/progenitor cells[J]. Methods Mol Biol, 2017, 1612:149-165.
8	Savage P. Chemotherapy curable malignancies and cancer stem cells:a biological review and hypothesis[J]. BMC Cancer, 2016, 16(1): 906.
9	Masciale V, Grisendi G, Banchelli F, et al. Isolation and identification of cancer stem-like cells in adenocarcinoma and squamous cell carcinoma of the lung: a pilot study[J]. Front Oncol, 2019, 9:1394-1406.
10	Wang Y, Jiang M, Du C, et al. Utilization of lung cancer cell lines for the study of lung cancer stem cells (Review)[J]. Oncol Lett, 2018, 15(5):6791-6798.
11	Liu X, Wei H, Liu Y, et al. Construction of high sensitive CD133 immune plga magnetic spheres platform for lung cancer stem cells isolation and its property evaluation[J]. J Biomed Nanotechnol, 2018, 14(6):1066-1074.
12	郑少秋, 李书华, 王红艳, 等. CD133阳性/阴性肺癌细胞的分类、鉴定及差异基因的筛选[J]. 中国肺癌杂志, 2015, 18(3):123-131.
13	Xie T, Mo L, Li L, et al. Identification of side population cells in human lung adenocarcinoma A549 cell line and elucidation of the underlying roles in lung cancer[J]. Oncol Lett, 2018, 15(4):4900-4906.
14	Bagheri V, Memar B, Behzadi R, et al. Isolation and identification of chemotherapy-enriched sphere-forming cells from a patient with gastric cancer[J]. J Cell Physiol, 2018, 233(10):7036-7046.
15	Roy S, Lu K, Nayak MK, et al. Activation of D2 dopamine receptors in CD133+ve cancer stem cells in non-small cell lung carcinoma inhibits proliferation, clonogenic ability, and invasiveness of these cells[J]. J Biol Chem, 2017, 292(2):435-445.
16	Roudi R, Korourian A, Shariftabrizi A, et al. Differential expression of cancer stem cell markers ALDH1 and CD133 in various lung cancer subtypes[J]. Cancer Invest, 2015, 33(7):294-302.
17	Alama A, Gangemi R, Ferrini S, et al. CD133-positive cells from non-small cell lung cancer show distinct sensitivity to cisplatin and afatinib[J]. Arch Immunol Ther Exp, 2015, 63(3):207-214.
18	Dan W, Wen GM, Wei H, et al. The roles of CD133 expression in the patients with non-small cell lung cancer[J]. Cancer Biomarkers, 2018, 22(3):385-394.
19	Chen E, Zeng Z, Bai B, et al. The prognostic value of CSCs biomarker CD133 in NSCLC: a meta-analysis[J]. Oncotarget, 2016, 7(35):56526-56539.
20	Dinavahi SS, Bazewicz CG, Gowda R, et al. Aldehyde Dehydrogenase Inhibitors for Cancer Therapeutics[J]. Trends Pharmacol Sci, 2019, 40(10):774-789.
21	Tian S, Xing Y, Xia P. The prognostic roles of circulating ALDH1⁺ tumor cell in the patients with non-small cell lung cancer[J]. Biosci Rep, 2018, 38(5):1-7.
22	Lei H, Zhang K, Wang CH, et al. Aldehyde dehydrogenase 1A1 confers erlotinib resistance via facilitating the reactive oxygen species-reactive carbonyl species metabolic pathway in lung adenocarcinomas[J]. Theranostics, 2019, 9(24):7122-7139.
23	Yun X, Zhang K, Wang J, et al. Targeting USP22 suppresses tumorigenicity and enhances cisplatin sensitivity through ALDH1A3 downregulation in cancer-initiating cells from lung adenocarcinoma[J]. Mol Cancer Res, 2018, 16(7):1161-1171.
24	Victor, Heurtier, Nick, et al. The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells[J]. Nat Commun, 2019, 10(1):1109-1124.
25	Lee S-H, Chen T-Y, Dhar SS, et al. A feedback loop comprising PRMT7 and miR-24-2 interplays with Oct4, Nanog, Klf4 and c-Myc to regulate stemness[J]. Nucleic Acids Res, 2016, 44(22):10603-10618.
26	Yun HS, Baek J-H, Yim J-H, et al. Radiotherapy diagnostic biomarkers in radioresistant human H460 lung cancer stem-like cells[J]. Cancer Biol Ther, 2016, 17(2):208-218.
27	Suresh R, Ali S, Ahmad A, et al. The role of cancer stem cells in recurrent and drug-resistant lung cancer[J]. Adv Exp Med Biol, 2015, 890(3):57-74.
28	Ye T, Li J, Sun Z, et al. Nr5a2 promotes cancer stem cell properties and tumorigenesis in nonsmall cell lung cancer by regulating Nanog[J]. Cancer Med, 2019, 8(3):1232-1245.
29	Hu F, Li C, Zheng X, et al. Lung adenocarcinoma resistance to therapy with EGFRtyrosine kinase inhibitors is related to increased expression of cancer stem cell markers SOX2, OCT4 and NANOG[J]. Oncol Rep, 2019, 43(2):727-735.
30	Macdonagh L, Gray SG, Breen EP, et al. Lung cancer stem cells: The root of resistance[J]. Cancer Lett, 2016, 372(2):147-156.
31	Dai Y, Liu S, Zhang W-Q, et al. YAP1 regulates ABCG2 and cancer cell side population in human lung cancer cells[J]. Oncotarget, 2017, 8(3):4096-4109.
32	Srinivas US, Tan BWQ, Vellayappan BA, et al. ROS and the DNA damage response in cancer[J]. Redox Biol, 2019, 25:101084-101093.
33	Morgan MA, Lawrence TS. Molecular pathways: Overcoming radiation resistance by targeting dna damage response pathways[J]. Clin Cancer Res, 2015, 21(13):2898-2904.
34	Philchenkov A. Radiation-induced cell death: signaling and pharmacological modulation[J]. Crit Rev Oncog, 2018, 23(1-2):13-37.
35	Jiang W, Jin G, Cai F, et al. Extracellular signal-regulated kinase 5 increases radioresistance of lung cancer cells by enhancing the DNA damage response[J]. Exp Mol Med, 2019, 51(2):1-20.
36	Chen X, Qian D, Cheng J, et al. High expression of Rad51c predicts poor prognostic outcome and induces cell resistance to cisplatin and radiation in non-small cell lung cancer[J]. Tumour Biol, 2016, 37(10):13489-13498.
37	Desai A, Webb B, Gerson SL. CD133⁺ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells[J]. Radiother Oncol, 2014, 110(3):538-545.
38	Chen Y, Zhang F, Tsai Y, et al. IL-6 signaling promotes DNA repair and prevents apoptosis in CD133⁺ stem-like cells of lung cancer after radiation[J]. Radiat Oncol, 2015, 10(1):227-227.
39	Barker HE, Patel R, Mclaughlin M, et al. CHK1 inhibition radiosensitises head and neck cancers to paclitaxel-based chemoradiotherapy[J]. Mol Cancer Ther, 2016, 15(9):2042-2054.
40	Fernandez HR, Gadre SM, Tan M, et al. The mitochondrial citrate carrier, SLC25A1, drives stemness and therapy resistance in non-small cell lung cancer[J]. Cell Death Differ, 2018, 25(7):1239-1258.
41	Li J, Jiang E, Wang X, et al. Dormant cells: the original cause of tumor recurrence and metastasis[J]. Cell Biochem Biophys, 2015, 72(2):317-320.
42	Endo H, Okami J, Okuyama H, et al. The induction of MIG6 under hypoxic conditions is critical for dormancy in primary cultured lung cancer cells with activating EGFR mutations[J]. Oncogene, 2017, 36(20):2824-2834.
43	Bridges KA, Chen X, Liu H, et al. MK-8776, a novel chk1 kinase inhibitor, radiosensitizes p53-defective human tumor cells[J]. Oncotarget, 2016, 7(44):71660-71672.
44	Skvortsova I, Debbage P, Kumar V, et al. Radiation resistance: Cancer stem cells (CSCs) and their enigmatic pro-survival signaling[J]. Semin Cancer Biol, 2015, 35:39-44.
45	Zhu L, Xue F, Xu X, et al. MicroRNA-198 inhibition of HGF/c-MET signaling pathway overcomes resistance to radiotherapy and induces apoptosis in human non-small-cell lung cancer[J]. J Cell Biochem, 2018, 119(9):7873-7886.
46	Chen P, Huang H, Wang Y, et al. Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death[J]. J Exp Clin Cancer Res, 2019, 38(1):254-271.
47	Liu G, Fen P, Fengqing Y, et al. Role of autophagy and apoptosis in non-small-cell lung cancer[J]. Int J Mol Sci, 2017, 18(2):367-391.
48	Saleh T, Cuttino L W, Gewirtz D A, et al. Autophagy is not uniformly cytoprotective: a personalized medicine approach for autophagy inhibition as a therapeutic strategy in non-small cell lung cancer[J]. Biochim Biophys Acta, 2016, 1860(10):2130-2136.
49	Liu Z, Huang S. Inhibition of miR-191 contributes to radiation-resistance of two lung cancer cell lines by altering autophagy activity[J]. Cancer Cell Int, 2015, 15(1):16.
50	Cechakova L, Ondrej M, Pavlik V, et al. A potent autophagy inhibitor (Lys05) enhances the impact of ionizing radiation on human lung cancer cells H1299[J]. Int J Mol Sci, 2019, 20(23):5881-5897.
51	Wen J, Liu H, Wang L, et al. Potentially Functional variants of ATG16L2 predict radiation pneumonitis and outcomes in patients with non-small cell lung cancer after definitive radiotherapy[J]. J Thorac Oncol, 2018, 13(5):660-675.
52	Chen N, Wu L, Yuan H, et al. ROS/Autophagy/Nrf2 pathway mediated Low-Dose radiation induced radio-resistance in human lung adenocarcinoma A549 cell[J]. Int J Biol Sci, 2015, 11(7): 833-844.
53	Elming P, Sørensen B, Oei A, et al. Hyperthermia: the optimal treatment to overcome radiation resistant hypoxia[J]. Cancers, 2019, 11(1):60-80.
54	Chatterjee S, Sil PC. Targeting the crosstalks of Wnt pathway with Hedgehog and Notch for cancer therapy[J]. Pharmacol Res, 2019, 142:251-261.
55	Schoning J, Monteiro M J, Gu W, et al. Drug resistance and cancer stem cells: the shared but distinct roles of hypoxia-inducible factors HIF1α and HIF2α[J]. Clin Exp Pharmacol Physiol, 2017, 44(2):153-161.
56	Christophe D, Vanessa D, Jorrit DW, et al. Hypoxia-induced cisplatin resistance in non-small cell lung cancer cells is mediated by HIF-1α and mutant p53 and can be overcome by induction of oxidative stress[J]. Cancers, 2018, 10(4):126-141.
57	Jiang ZF, Wang M, Xu JL, et al. Hypoxia promotes mitochondrial glutamine metabolism through HIF1α-GDH pathway in human lung cancer cells[J]. Biochem Biophys Res Commun, 2017, 483(1):32-38.
58	He J, Hu Y, Hu M, et al. The relationship between the preoperative plasma level of HIF-1α and clinic pathological features, prognosis in non-small cell lung cancer[J]. Sci Rep, 2016, 6(1):20586-20598.
59	Peng J, Wang X, Ran L, et al. Hypoxia-inducible factor 1α regulates the transforming growth factor β1/SMAD family member 3 pathway to promote breast cancer progression[J]. J Breast Cancer, 2018, 21(3):259-266.
60	Berezowska S, Galván JA, Langer R, et al. Glycine decarboxylase and HIF-1α expression are negative prognostic factors in primary resected early-stage non-small cell lung cancer[J]. Virchows Archiv, 2017, 470(3):323-330.
61	Gao X, Wang G, Zhao W, et al. Blocking OLFM4/HIF-1α axis alleviates hypoxia-induced invasion, epithelial-mesenchymal transition, and chemotherapy resistance in non-small-cell lung cancer[J]. J Cell Physiol, 2019, 234(9):15035-15043.
62	Yu Y, Wang Y, Wang Y, et al. Antiangiogenic therapy using endostatin increases the number of ALDH⁺ lung cancer stem cells by generating intratumor hypoxia[J]. Sci Rep, 2016, 6(1): 34239.

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