临床荟萃 ›› 2021, Vol. 36 ›› Issue (7): 659-663.doi: 10.3969/j.issn.1004-583X.2021.07.018
应勤健1, 苗贤媛2, 崔晓颖3, 龙丹4, 付志璇4, 罗聪4(
)
收稿日期:2021-03-15
出版日期:2021-07-20
发布日期:2021-08-02
通讯作者:
罗聪
E-mail:lw939291@126.com
基金资助:
Received:2021-03-15
Online:2021-07-20
Published:2021-08-02
摘要：
巢蛋白(Nestin)是一种细胞骨架蛋白,多表达于肿瘤新生血管内皮细胞表面。通过干预肿瘤血管的形成,Nestin能够促进肿瘤细胞的增殖、侵袭和转移,介导肿瘤的发生发展,与肿瘤患者的预后密切相关,因此,Nestin可能成为一种全新的抗肿瘤治疗靶点。研究发现在多种恶性肿瘤,如神经胶质瘤、肺癌、乳腺癌及结肠癌中,Nestin的表达均显著升高。本文将围绕Nestin的结构、基本功能及其在常见肿瘤发生发展中发挥的作用进行综述,为临床相关研究提供新的思路。
中图分类号:
应勤健, 苗贤媛, 崔晓颖, 龙丹, 付志璇, 罗聪. 巢蛋白与肿瘤发生发展[J]. 临床荟萃, 2021, 36(7): 659-663.
图1 巢蛋白分子的结构 橙色:N端区域的“头”;蓝色:α螺旋杆区的中央杆部;绿色:C端区域的“尾”
| [1] |
Sharma P, Alsharif S, Fallatah A, et al. Intermediate filaments as effectors of cancer development and metastasis: a focus on keratins, vimentin, and nestin[J]. Cells, 2019,8(5):497-518.
doi: 10.3390/cells8050497 URL |
| [2] |
Bernal A, Arranz L. Nestin-expressing progenitor cells: function, identity and therapeutic implications[J]. Cell Mol Life Sci, 2018,75(12):2177-2195.
doi: 10.1007/s00018-018-2794-z URL |
| [3] |
Krupkova O Jr, Loja T, Redova M, et al. Analysis of nuclear nestin localization in cell lines derived from neurogenic tumors[J]. Tumour Biol, 2011,32(4):631-639.
doi: 10.1007/s13277-011-0162-9 URL |
| [4] | Panvini FM, Pacini S, Montali M, et al. High nestin expression marks the endosteal capillary network in human bone marrow[J]. Front Cell Dev Biol, 2020,11(8):1-14. |
| [5] | Xie L, Zeng X, Hu J, et al. Characterization of nestin, a selective marker for bone marrow derived mesenchymal stem cells[J]. Stem Cells Int, 2015,7(6):1-9. |
| [6] | 罗时珂, 廖祥中, 谢东明, 等. 巢蛋白对缺血心肌损伤再修复影响[J]. 赣南医学院学报, 2017,37(2):199-202. |
| [7] | González-Hernández S, Gómez MJ, Sanchez-Cabo F, et al. Sox17 controls emergence and remodeling of nestin-expressing coronary vessels[J]. Circ Res, 2020,127(11):252-270. |
| [8] | Brassard-Jollive N, Muller MC, Germain S. In vitro 3D systems to model tumor angiogenesis and interactions with stromal cells[J]. Front Cell Dev Biol, 2020,11(8):1-16. |
| [9] |
Jiang X, Wang J, Deng X, et al. The role of microenvironment in tumor angiogenesis[J]. J Exp Clin Cancer Res, 2020,39(1):1-19.
doi: 10.1186/s13046-019-1487-2 URL |
| [10] |
Matsuda Y, Hagio M, Ishiwata T. Nestin: A novel angiogenesis marker and possible target for tumor angiogenesis[J]. World J Gastroenterol, 2013,19(1):42-48.
doi: 10.3748/wjg.v19.i1.42 URL |
| [11] | Klein D, Meissner N, Kleff V, et al. Nestin (+) tissue-resident multipotent stem cells contribute to tumor progression by differentiating into pericytes and smooth muscle cells resulting in blood vessel remodeling[J]. Front Oncol, 2014,1(4):169-180. |
| [12] | Onisim A, Achimas-Cadariu A, Vlad C, et al. Current insights into the association of nestin with tumor angiogenesis[J]. J BUON, 2015,20(3):699-706. |
| [13] | 林才厚, 陈建屏, 王春华, 等. ZEB1及Nestin在高级别胶质瘤初治及配对复发标本中的表达及临床意义[J]. 福建医科大学学报, 2018,52(6):359-363. |
| [14] | Zheng ZQ, Chen JT, Zheng MC, et al. Nestin +/CD31 + cells in the hypoxic perivascular niche regulate glioblastoma chemoresistance by upregulating JAG1 and DLL4[J]. Neuro Oncol, 2020,11(29):265. |
| [15] |
Matini AH, Naeini MM, Ardekani HP, et al. Evaluation of nestin and EGFR in patients with glioblastoma multiforme in a public hospital in Iran[J]. Asian Pac J Cancer Prev, 2020,21(10):2889-2894.
doi: 10.31557/APJCP.2020.21.10.2889 URL |
| [16] |
Wu B, Sun C, Feng F, et al. Do relevant markers of cancer stem cells CD133 and nestin indicate a poor prognosis in glioma patients? A systematic review and meta-analysis[J]. J Exp Clin Cancer Res, 2015,34(1):44-56.
doi: 10.1186/s13046-015-0163-4 URL |
| [17] |
Lu W J, Lan F, He Q, et al. Inducible expression of stem cell associated intermediate filament nestin reveals an important role in glioblastoma carcinogenesis[J]. Int J Cancer, 2011,128(2):343-351.
doi: 10.1002/ijc.v128:2 URL |
| [18] |
Zhang D, Wang J. Nestin is significantly associated with the overall survival of nonsmall cell lung cancer: A meta-analysis[J]. J Cancer Res Ther, 2020,16(4):800-803.
doi: 10.4103/0973-1482.204901 URL |
| [19] |
Li S, Lai Y, Fan J, et al. Clinicopathological and prognostic significance of nestin expression in patients with non-small cell lung cancer: a systematic review and meta-analysis[J]. Clin Exp Med, 2017,17(2):161-174.
doi: 10.1007/s10238-016-0421-6 URL |
| [20] |
Singh S, Trevino J, Bora-Singhal N, et al. EGFR/Src/Akt signaling modulates SOX2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer[J]. Mol Cancer, 2012,11(1):73-88.
doi: 10.1186/1476-4598-11-73 URL |
| [21] |
Schaefer T, Lengerke C. SOX2 protein biochemistry in stemness, reprogramming, and cancer: the PI3K/AKT/SOX2 axis and beyond[J]. Oncogene, 2020,39(2):278-292.
doi: 10.1038/s41388-019-0997-x URL |
| [22] |
Schieber M, Chandel N. ROS function in redox signaling and oxidative stress[J]. Curr Biol, 2014,24(10):453-462.
doi: 10.1016/j.cub.2014.03.034 pmid: 24845678 |
| [23] |
Zhang DD. The Nrf2-Keap1-ARE signaling pathway: the regulation and dual function of Nrf2 in cancer[J]. Antioxid Redox Signal, 2010,13(11):1623-1626.
doi: 10.1089/ars.2010.3301 URL |
| [24] |
Panieri E, Saso L. Inhibition of the nrf2/keap1 axis: a promising therapeutic strategy to alter redox balance of cancer cells?[J]. Antioxid Redox Signal, 2021,34(18):1428-1483.
doi: 10.1089/ars.2020.8146 URL |
| [25] |
Wang J, Lu Q, Cai J, et al. Nestin regulates cellular redox homeostasis in lung cancer through the Keap1-Nrf2 feedback loop[J]. Nat Commun, 2019,10(1):5043-5060.
doi: 10.1038/s41467-019-12925-9 URL |
| [26] |
Takakuwa O, Maeno K, Kunii E, et al. Involvement of intermediate filament nestin in cell growth of small-cell lung cancer[J]. Lung Cancer, 2013,81(2):174-179.
doi: 10.1016/j.lungcan.2013.04.022 pmid: 23706418 |
| [27] | Zhang X, Xing C, Guan W, et al. Clinicopathological and prognostic significance of nestin expression in patients with breast cancer: A systematic review and meta-analysis[J]. Cancer Cell Int, 2020,5(20):169-186. |
| [28] | 黎胤谋, 李靖, 彭世军. Nestin在乳腺癌中的表达及其与他莫昔芬治疗疗效和预后的关系[J]. 国际肿瘤学杂志, 2019,46(4):205-210. |
| [29] |
Feng W, Liu S, Zhu R, et al. SOX10 induced nestin expression regulates cancer stem cell properties of TNBC cells[J]. Biochem Biophys Res Commun, 2017,485(2):522-528.
doi: 10.1016/j.bbrc.2017.02.014 URL |
| [30] | Tampaki EC, Tampakis A, Nonni A, et al. Nestin and cluster of differentiation 146 expression in breast cancer: Predicting early recurrence by targeting metastasis?[J]. Tumour Biol, 2017,39(3):1-10. |
| [31] |
Krüger K, Stefansson IM, Collett K, et al. Microvessel proliferation by co-expression of endothelial nestin and Ki-67 is associated with a basal-like phenotype and aggressive features in breast cancer[J]. Breast, 2013,22(3):282-288.
doi: 10.1016/j.breast.2012.07.008 pmid: 22840462 |
| [32] |
Aleksandra N, Jedrzej G, Maria P, et al. Nestin-positive microvessel density is an independent prognostic factor in breast cancer[J]. Int J Oncol, 2017,51(2):668-676.
doi: 10.3892/ijo.2017.4057 pmid: 28656248 |
| [33] |
Iwamoto T, Booser D, Valero V, et al. Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry[J]. J Clin Oncol, 2012,30(7):729-734.
doi: 10.1200/JCO.2011.36.2574 URL |
| [34] |
Sheffield BS, Kos Z, Asleh-Aburaya K, et al. Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor[J]. Breast Cancer Res Treat, 2016,155(3):483-490.
doi: 10.1007/s10549-016-3689-z URL |
| [35] | Won JR, Gao D, Chow C, et al. A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard[J]. Mod Pathol, 2013,26(11):1438-1450. |
| [36] |
Asleh-Aburaya K, Sheffield BS, Kos Z, et al. Basal biomarkers nestin and INPP4b identify intrinsic subtypes accurately in breast cancers that are weakly positive for oestrogen receptor[J]. Histopathology, 2017,70(2):185-194.
doi: 10.1111/his.13038 pmid: 27402148 |
| [37] |
Meisen WH, Dubin S, Sizemore ST, et al. Changes in BAI1 and nestin expression are prognostic indicators for survival and metastases in breast cancer and provide opportunities for dual targeted therapies[J]. Mol Cancer Ther, 2015,14(1):307-314.
doi: 10.1158/1535-7163.MCT-14-0659 URL |
| [38] |
Yoo JY, Haseley A, Bratasz A, et al. Antitumor efficacy of 34.5ENVE: a transcriptionally retargeted and “Vstat120”-expressing oncolytic virus[J]. Mol Ther, 2012,20(2):287-297.
doi: 10.1038/mt.2011.208 URL |
| [39] |
Asleh K, Lyck Carstensen S, Tykjaer Jørgensen CL, et al. Basal biomarkers nestin and INPP4B predict gemcitabine benefit in metastatic breast cancer: Samples from the phase III SBG0102 clinical trial[J]. Int J Cancer, 2019,144(10):2578-2586.
doi: 10.1002/ijc.v144.10 URL |
| [40] | Vila AL, Leyva A, Julián Vargas Flores, et al. GIST associated with von recklinghausen disease: report of two cases and review of literature[J]. Ann Med Surg (Lond), 2021,1(62):365-368. |
| [41] |
Wang J, Cai J, Huang Y, et al. Nestin regulates proliferation and invasion of gastrointestinal stromal tumor cells by altering mitochondrial dynamics[J]. Oncogene, 2016,35(24):3139-3150.
doi: 10.1038/onc.2015.370 pmid: 26434586 |
| [42] |
Kelly CM, Sainz LG, Chi P. The management of metastatic GIST: current standard and investigational therapeutics[J]. J Hematol Oncol, 2021,14(1):2-14.
doi: 10.1186/s13045-020-01026-6 URL |
| [43] | Terada T. Smooth muscles and stem cells of embryonic guts express KIT, PDGFRRA, CD34 and many other stem cell antigens: suggestion that GIST arise from smooth muscles and gut stem cells[J]. Int J Clin Exp Pathol, 2013,6(6):1038-1045. |
| [44] | 冯菲, 马大烈, 刘伟强, 等. 巢蛋白(Nestin)在胃肠道间质瘤组织中的表达及其临床意义[J]. 实用癌症杂志, 2004,19(1):24-26. |
| [45] | 孟鑫, 杜金荣. p53、p21、Nestin在胃肠道间质肿瘤的表达研究[J]. 齐齐哈尔医学院学报, 2010,31(16):15-16. |
| [46] | Li J, Wang R, Yang L, et al. Knockdown of nestin inhibits proliferation and migration of colorectal cancer cells[J]. Int J Clin Exp Pathol, 2015,8(6):6377-6386. |
| [47] |
Mariusz C, Aleksandra N, Jedrzej G, et al. Comparison of microvessel density using nestin and CD34 in colorectal cancer[J]. Anticancer Res, 2018,38(7):3889-3895.
doi: 10.21873/anticanres.12673 URL |
| [1] | 唐旭, 左庄, 杨凯, 张志源, 王淇, 董信春, 苟云久. 抗血管生成药物联合化疗对恶性胸膜间皮瘤的疗效和安全性:更新的系统评价与meta分析[J]. 临床荟萃, 2025, 40(4): 304-312. |
| [2] | 张森, 张新生, 王东祥. 多层螺旋CT联合血清Vanin-1水平预测COPD患者预后的临床价值[J]. 临床荟萃, 2025, 40(4): 339-343. |
| [3] | 王银峰, 李满祥. 曲拉西利联合化疗治疗广泛期小细胞肺癌1例并文献复习[J]. 临床荟萃, 2025, 40(4): 355-359. |
| [4] | 刘胜华. 稳定型心绞痛患者血尿酸水平与冠状动脉钙化程度的相关性[J]. 临床荟萃, 2025, 40(3): 211-216. |
| [5] | 冯雨慧, 邹兰兰, 崔晨航, 黄先杰, 乔俊英. 血清标志物联合检测对儿童呼吸窘迫综合征早期预测的临床价值[J]. 临床荟萃, 2025, 40(3): 237-242. |
| [6] | 黄兴舟, 郑卫华, 张树桐, 陈燕浩. 载药微球与常规支气管动脉化疗栓塞术治疗晚期非小细胞肺癌的临床疗效及安全性对比[J]. 临床荟萃, 2025, 40(3): 243-250. |
| [7] | 李忠标, 赵习浩, 杜敏, 王江, 于跃, 张佃良. 肠腔内生性卵巢外腹膜浆液性乳头状腺癌1例并文献复习[J]. 临床荟萃, 2025, 40(3): 257-261. |
| [8] | 季万里, 马周, 石郁喜, 孙为生. 青年脊髓硬脊膜动静脉瘘1例并文献复习[J]. 临床荟萃, 2025, 40(3): 262-265. |
| [9] | 陈天浩, 黄正. 慢性肾脏病3~5期患者血清维生素K2检测的临床意义[J]. 临床荟萃, 2025, 40(2): 122-127. |
| [10] | 陈哲宇, 何倩倩, 郭小冬, 王环环, 杨艳丽, 阿赛古丽. 以皮肤多发转移灶为首发表现的肺小细胞癌:1例罕见病例报道[J]. 临床荟萃, 2025, 40(1): 65-69. |
| [11] | 张雪, 王俊祥. 类风湿关节炎共病的研究进展[J]. 临床荟萃, 2025, 40(1): 86-89. |
| [12] | 韩铠阳, 冯铜铜, 包瑛. 儿童狼疮性肾炎合并神经精神狼疮的临床特征和危险因素[J]. 临床荟萃, 2024, 39(9): 812-815. |
| [13] | 散丹, 甄瑾. 脊髓硬脊膜动静脉瘘1例并文献复习[J]. 临床荟萃, 2024, 39(9): 825-827. |
| [14] | 马苗苗, 王义艳, 温甜甜, 马丽群. 甘油三酯-葡萄糖指数与阻塞性睡眠呼吸暂停综合征相关性的研究进展[J]. 临床荟萃, 2024, 39(9): 851-854. |
| [15] | 张中楼, 崔坤, 孟晋启. 运动保护心血管系统的研究进展[J]. 临床荟萃, 2024, 39(9): 855-860. |
| 阅读次数 | ||||||
|
全文 |
|
|||||
|
摘要 |
|
|||||
